Abstract
RecQ DNA helicases are critical for proper maintenance of genomic stability, and mutations in multiple human RecQ genes are linked with genetic disorders characterized by a predisposition to cancer. RecQ proteins are conserved from prokaryotes to humans and in all cases form higher-order complexes with other proteins to efficiently execute their cellular functions. The focus of this review is a conserved complex that is formed between RecQ helicases and type-I topoisomerases. In humans, this complex is referred to as the BLM dissolvasome or BTR complex, and is comprised of the RecQ helicase BLM, topoisomerase IIIα, and the RMI proteins. The BLM dissolvasome functions to resolve linked DNA intermediates without exchange of genetic material, which is critical in somatic cells. We will review the history of this complex and highlight its roles in DNA replication, recombination, and repair. Additionally, we will review recently established interactions between BLM dissolvasome and a second set of genome maintenance factors (the Fanconi anemia proteins) that appear to allow coordinated genome maintenance efforts between the two systems.
Similar content being viewed by others
References
Loeb LA (2001) A mutator phenotype in cancer. Cancer Res 61(8):3230–3239
Ouyang KJ, Woo LL, Ellis NA (2008) Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases. Mech Ageing Dev 129(7–8):425–440
Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396(6712):643–649
Bachrati CZ, Hickson ID (2003) RecQ helicases: suppressors of tumorigenesis and premature aging. Biochem J 374(Pt 3):577–606
Bachrati CZ, Hickson ID (2008) RecQ helicases: guardian angels of the DNA replication fork. Chromosoma 117(3):219–233
Mankouri HW, Hickson ID (2007) The RecQ helicase-topoisomerase III-Rmi1 complex: a DNA structure-specific ‘dissolvasome’? Trends Biochem Sci 32(12):538–546
Bloom D (1954) Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. Am J Dis Child 88(6):754–758
German J (1993) Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine (Baltimore) 72(6):393–406
Chu WK, Hickson ID (2009) RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer 9(9):644–654
Rosin MP, German J (1985) Evidence for chromosome instability in vivo in Bloom syndrome: increased numbers of micronuclei in exfoliated cells. Hum Genet 71(3):187–191
Chaganti RS, Schonberg S, German J (1974) A manyfold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes. Proc Natl Acad Sci USA 71(11):4508–4512
McDaniel LD, Schultz RA (1992) Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15. Proc Natl Acad Sci USA 89(17):7968–7972
Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M, German J (1995) The Bloom’s syndrome gene product is homologous to RecQ helicases. Cell 83(4):655–666
German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA (2007) Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Hum Mutat 28(8):743–753
Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Gueret M (1997) Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom’s syndrome. Hum Mol Genet 6(9):1427–1434
Barakat A, Ababou M, Onclercq R, Dutertre S, Chadli E, Hda N, Benslimane A, Amor-Gueret M (2000) Identification of a novel BLM missense mutation (2,706T>C) in a Moroccan patient with Bloom’s syndrome. Hum Mutat 15(6):584–585
Guo RB, Rigolet P, Ren H, Zhang B, Zhang XD, Dou SX, Wang PY, Amor-Gueret M, Xi XG (2007) Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein. Nucleic Acids Res 35(18):6297–6310
Neff NF, Ellis NA, Ye TZ, Noonan J, Huang K, Sanz M, Proytcheva M (1999) The DNA helicase activity of BLM is necessary for the correction of the genomic instability of Bloom syndrome cells. Mol Biol Cell 10(3):665–676
Bahr A, De Graeve F, Kedinger C, Chatton B (1998) Point mutations causing Bloom’s syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene 17(20):2565–2571
Bernstein DA, Zittel MC, Keck JL (2003) High-resolution structure of the E. coli RecQ helicase catalytic core. EMBO J 22(19):4910–4921
Nakayama H, Nakayama K, Nakayama R, Irino N, Nakayama Y, Hanawalt PC (1984) Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway. Mol Gen Genet 195(3):474–480
Nakayama K, Irino N, Nakayama H (1985) The recQ gene of Escherichia coli K12: molecular cloning and isolation of insertion mutants. Mol Gen Genet 200(2):266–271
Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD (1996) Positional cloning of the Werner’s syndrome gene. Science 272(5259):258–262
Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y (1999) Mutations in RECQL4 cause a subset of cases of Rothmund–Thomson syndrome. Nat Genet 22(1):82–84
Siitonen HA, Kopra O, Kaariainen H, Haravuori H, Winter RM, Saamanen AM, Peltonen L, Kestila M (2003) Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum Mol Genet 12(21):2837–2844
Van Maldergem L, Siitonen HA, Jalkh N, Chouery E, De Roy M, Delague V, Muenke M, Jabs EW, Cai J, Wang LL, Plon SE, Fourneau C, Kestila M, Gillerot Y, Megarbane A, Verloes A (2006) Revisiting the craniosynostosis-radial ray hypoplasia association: Baller–Gerold syndrome caused by mutations in the RECQL4 gene. J Med Genet 43(2):148–152
Killoran MP, Keck JL (2006) Sit down, relax and unwind: structural insights into RecQ helicase mechanisms. Nucleic Acids Res 34(15):4098–4105
Morozov V, Mushegian AR, Koonin EV, Bork P (1997) A putative nucleic acid-binding domain in Bloom’s and Werner’s syndrome helicases. Trends Biochem Sci 22(11):417–418
Pike AC, Shrestha B, Popuri V, Burgess-Brown N, Muzzolini L, Costantini S, Vindigni A, Gileadi O (2009) Structure of the human RECQ1 helicase reveals a putative strand-separation pin. Proc Natl Acad Sci USA 106(4):1039–1044
Kitano K, Kim SY, Hakoshima T (2010) Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN. Structure 18(2):177–187
von Kobbe C, Thoma NH, Czyzewski BK, Pavletich NP, Bohr VA (2003) Werner syndrome protein contains three structure-specific DNA binding domains. J Biol Chem 278(52):52997–53006
Huber MD, Duquette ML, Shiels JC, Maizels N (2006) A conserved G4 DNA binding domain in RecQ family helicases. J Mol Biol 358(4):1071–1080
Vindigni A, Hickson ID (2009) RecQ helicases: multiple structures for multiple functions? HFSP J 3(3):153–164
Bernstein DA, Keck JL (2005) Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain. Structure 13(8):1173–1182
Kitano K, Yoshihara N, Hakoshima T (2007) Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. J Biol Chem 282(4):2717–2728
Sato A, Mishima M, Nagai A, Kim SY, Ito Y, Hakoshima T, Jee JG, Kitano K (2010) Solution structure of the HRDC domain of human Bloom syndrome protein BLM. J Biochem 148(4):517–525
Wu L, Chan KL, Ralf C, Bernstein DA, Garcia PL, Bohr VA, Vindigni A, Janscak P, Keck JL, Hickson ID (2005) The HRDC domain of BLM is required for the dissolution of double Holliday junctions. EMBO J 24(14):2679–2687
Karow JK, Chakraverty RK, Hickson ID (1997) The Bloom’s syndrome gene product is a 3′–5′ DNA helicase. J Biol Chem 272(49):30611–30614
Sun H, Karow JK, Hickson ID, Maizels N (1998) The Bloom’s syndrome helicase unwinds G4 DNA. J Biol Chem 273(42):27587–27592
Huber MD, Lee DC, Maizels N (2002) G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition. Nucleic Acids Res 30(18):3954–3961
Mohaghegh P, Karow JK, Brosh RM Jr, Bohr VA, Hickson ID (2001) The Bloom’s and Werner’s syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res 29(13):2843–2849
Popuri V, Bachrati CZ, Muzzolini L, Mosedale G, Costantini S, Giacomini E, Hickson ID, Vindigni A (2008) The human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. J Biol Chem 283(26):17766–17776
van Brabant AJ, Ye T, Sanz M, German IJ, Ellis NA, Holloman WK (2000) Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry 39(47):14617–14625
Karow JK, Newman RH, Freemont PS, Hickson ID (1999) Oligomeric ring structure of the Bloom’s syndrome helicase. Curr Biol 9(11):597–600
Beresten SF, Stan R, van Brabant AJ, Ye T, Naureckiene S, Ellis NA (1999) Purification of overexpressed hexahistidine-tagged BLM N431 as oligomeric complexes. Protein Expr Purif 17(2):239–248
Xu YN, Bazeille N, Ding XY, Lu XM, Wang PY, Bugnard E, Grondin V, Dou SX, Xi XG (2012) Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures. Nucleic Acids Res 40(19):9802–9814
Muzzolini L, Beuron F, Patwardhan A, Popuri V, Cui S, Niccolini B, Rappas M, Freemont PS, Vindigni A (2007) Different quaternary structures of human RECQ1 are associated with its dual enzymatic activity. PLoS Biol 5(2):e20
Xue Y, Ratcliff GC, Wang H, Davis-Searles PR, Gray MD, Erie DA, Redinbo MR (2002) A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3′–5′ exonuclease and 5′-protruding strand endonuclease activities. Biochemistry 41(9):2901–2912
Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD (2008) The Werner syndrome protein binds replication fork and Holliday junction DNAs as an oligomer. J Biol Chem 283(36):24478–24483
Huang S, Beresten S, Li B, Oshima J, Ellis NA, Campisi J (2000) Characterization of the human and mouse WRN 3′–5′ exonuclease. Nucleic Acids Res 28(12):2396–2405
Harmon FG, Kowalczykowski SC (2001) Biochemical characterization of the DNA helicase activity of the Escherichia coli RecQ helicase. J Biol Chem 276(1):232–243
Janscak P, Garcia PL, Hamburger F, Makuta Y, Shiraishi K, Imai Y, Ikeda H, Bickle TA (2003) Characterization and mutational analysis of the RecQ core of the bloom syndrome protein. J Mol Biol 330(1):29–42
Brosh RM Jr, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA (2000) Replication protein A physically interacts with the Bloom’s syndrome protein and stimulates its helicase activity. J Biol Chem 275(31):23500–23508
Cheok CF, Wu L, Garcia PL, Janscak P, Hickson ID (2005) The Bloom’s syndrome helicase promotes the annealing of complementary single-stranded DNA. Nucleic Acids Res 33(12):3932–3941
Umezu K, Nakayama H (1993) RecQ DNA helicase of Escherichia coli. Characterization of the helix-unwinding activity with emphasis on the effect of single-stranded DNA-binding protein. J Mol Biol 230(4):1145–1150
Harmon FG, Kowalczykowski SC (1998) RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA recombination. Genes Dev 12(8):1134–1144
Shereda RD, Bernstein DA, Keck JL (2007) A central role for SSB in Escherichia coli RecQ DNA helicase function. J Biol Chem 282(26):19247–19258
Lecointe F, Serena C, Velten M, Costes A, McGovern S, Meile JC, Errington J, Ehrlich SD, Noirot P, Polard P (2007) Anticipating chromosomal replication fork arrest: SSB targets repair DNA helicases to active forks. EMBO J 26(19):4239–4251
Shereda RD, Reiter NJ, Butcher SE, Keck JL (2009) Identification of the SSB binding site on E. coli RecQ reveals a conserved surface for binding SSB’s C terminus. J Mol Biol 386(3):612–625
Cejka P, Kowalczykowski SC (2010) The full-length Saccharomyces cerevisiae Sgs1 protein is a vigorous DNA helicase that preferentially unwinds Holliday junctions. J Biol Chem 285(11):8290–8301
Cobb JA, Bjergbaek L, Shimada K, Frei C, Gasser SM (2003) DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. EMBO J 22(16):4325–4336
Hegnauer AM, Hustedt N, Shimada K, Pike BL, Vogel M, Amsler P, Rubin SM, van Leeuwen F, Guenole A, van Attikum H, Thoma NH, Gasser SM (2012) An N-terminal acidic region of Sgs1 interacts with Rpa70 and recruits Rad53 kinase to stalled forks. EMBO J 31(18):3768–3783
Garcia PL, Bradley G, Hayes CJ, Krintel S, Soultanas P, Janscak P (2004) RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages on DNA unwinding by BLM and WRN helicases. Nucleic Acids Res 32(12):3771–3778
Doherty KM, Sommers JA, Gray MD, Lee JW, von Kobbe C, Thoma NH, Kureekattil RP, Kenny MK, Brosh RM Jr (2005) Physical and functional mapping of the replication protein a interaction domain of the Werner and Bloom syndrome helicases. J Biol Chem 280(33):29494–29505
Ahn B, Lee JW, Jung H, Beck G, Bohr VA (2009) Mechanism of Werner DNA helicase: POT1 and RPA stimulates WRN to unwind beyond gaps in the translocating strand. PLoS ONE 4(3):e4673
Sowd G, Wang H, Pretto D, Chazin WJ, Opresko PL (2009) Replication protein A stimulates the Werner syndrome protein branch migration activity. J Biol Chem 284(50):34682–34691
Machwe A, Lozada E, Wold MS, Li GM, Orren DK (2011) Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage. J Biol Chem 286(5):3497–3508
Hyun M, Park S, Kim E, Kim DH, Lee SJ, Koo HS, Seo YS, Ahn B (2012) Physical and functional interactions of Caenorhabditis elegans WRN-1 helicase with RPA-1. Biochemistry 51(7):1336–1345
Cui S, Arosio D, Doherty KM, Brosh RM Jr, Falaschi A, Vindigni A (2004) Analysis of the unwinding activity of the dimeric RECQ1 helicase in the presence of human replication protein A. Nucleic Acids Res 32(7):2158–2170
Cui S, Klima R, Ochem A, Arosio D, Falaschi A, Vindigni A (2003) Characterization of the DNA-unwinding activity of human RECQ1, a helicase specifically stimulated by human replication protein A. J Biol Chem 278(3):1424–1432
Garcia PL, Liu Y, Jiricny J, West SC, Janscak P (2004) Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a single polypeptide. EMBO J 23(14):2882–2891
Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID (2000) The Bloom’s syndrome gene product interacts with topoisomerase III. J Biol Chem 275(13):9636–9644
Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W (2005) BLAP75, an essential component of Bloom’s syndrome protein complexes that maintain genome integrity. EMBO J 24(7):1465–1476
Bhattacharyya S, Keirsey J, Russell B, Kavecansky J, Lillard-Wetherell K, Tahmaseb K, Turchi JJ, Groden J (2009) Telomerase-associated protein 1, HSP90, and topoisomerase IIalpha associate directly with the BLM helicase in immortalized cells using ALT and modulate its helicase activity using telomeric DNA substrates. J Biol Chem 284(22):14966–14977
Ke Y, Huh JW, Warrington R, Li B, Wu N, Leng M, Zhang J, Ball HL, Yu H (2011) PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution. EMBO J 30(16):3309–3321
Wu L, Davies SL, Levitt NC, Hickson ID (2001) Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J Biol Chem 276(22):19375–19381
Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC (2008) Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci USA 105(44):16906–16911
Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC (2011) BLM–DNA2–RPA–MRN and EXO1–BLM–RPA–MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev 25(4):350–362
Suhasini AN, Rawtani NA, Wu Y, Sommers JA, Sharma S, Mosedale G, North PS, Cantor SB, Hickson ID, Brosh RM Jr (2011) Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom’s syndrome. EMBO J 30(4):692–705
Xu D, Muniandy P, Leo E, Yin J, Thangavel S, Shen X, Ii M, Agama K, Guo R, Fox D 3rd, Meetei AR, Wilson L, Nguyen H, Weng NP, Brill SJ, Li L, Vindigni A, Pommier Y, Seidman M, Wang W (2010) Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J 29(18):3140–3155
Beamish H, Kedar P, Kaneko H, Chen P, Fukao T, Peng C, Beresten S, Gueven N, Purdie D, Lees-Miller S, Ellis N, Kondo N, Lavin MF (2002) Functional link between BLM defective in Bloom’s syndrome and the ataxia-telangiectasia-mutated protein, ATM. J Biol Chem 277(34):30515–30523
Davies SL, North PS, Dart A, Lakin ND, Hickson ID (2004) Phosphorylation of the Bloom’s syndrome helicase and its role in recovery from S-phase arrest. Mol Cell Biol 24(3):1279–1291
Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM Jr (2004) Stimulation of flap endonuclease-1 by the Bloom’s syndrome protein. J Biol Chem 279(11):9847–9856
Wang W, Bambara RA (2005) Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure. J Biol Chem 280(7):5391–5399
Selak N, Bachrati CZ, Shevelev I, Dietschy T, van Loon B, Jacob A, Hubscher U, Hoheisel JD, Hickson ID, Stagljar I (2008) The Bloom’s syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta. Nucleic Acids Res 36(16):5166–5179
Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K, Kunkel TA, Groden J (2001) The Bloom’s syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. J Biol Chem 276(32):30031–30035
Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL, Ryu GH, Freire R, Hickson ID, Jiricny J, Stagljar I (2001) Direct association of Bloom’s syndrome gene product with the human mismatch repair protein MLH1. Nucleic Acids Res 29(21):4378–4386
Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC (2001) Functional interaction of p53 and BLM DNA helicase in apoptosis. J Biol Chem 276(35):32948–32955
Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV (2001) The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Oncogene 20(57):8276–8280
von Kobbe C, Karmakar P, Dawut L, Opresko P, Zeng X, Brosh RM Jr, Hickson ID, Bohr VA (2002) Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins. J Biol Chem 277(24):22035–22044
Stavropoulos DJ, Bradshaw PS, Li X, Pasic I, Truong K, Ikura M, Ungrin M, Meyn MS (2002) The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Hum Mol Genet 11(25):3135–3144
Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA (2002) Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 277(43):41110–41119
Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65:635–692
Gangloff S, McDonald JP, Bendixen C, Arthur L, Rothstein R (1994) The yeast type-I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol 14(12):8391–8398
Bennett RJ, Noirot-Gros MF, Wang JC (2000) Interaction between yeast sgs1 helicase and DNA topoisomerase III. J Biol Chem 275(35):26898–26905
Fricke WM, Kaliraman V, Brill SJ (2001) Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase. J Biol Chem 276(12):8848–8855
Bennett RJ, Wang JC (2001) Association of yeast DNA topoisomerase III and Sgs1 DNA helicase: studies of fusion proteins. Proc Natl Acad Sci USA 98(20):11108–11113
Harmon FG, DiGate RJ, Kowalczykowski SC (1999) RecQ helicase and topoisomerase III comprise a novel DNA strand passage function: a conserved mechanism for control of DNA recombination. Mol Cell 3(5):611–620
Suski C, Marians KJ (2008) Resolution of converging replication forks by RecQ and topoisomerase III. Mol Cell 30(6):779–789
Harmon FG, Brockman JP, Kowalczykowski SC (2003) RecQ helicase stimulates both DNA catenation and changes in DNA topology by topoisomerase III. J Biol Chem 278(43):42668–42678
Johnson FB, Lombard DB, Neff NF, Mastrangelo MA, Dewolf W, Ellis NA, Marciniak RA, Yin Y, Jaenisch R, Guarente L (2000) Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells. Cancer Res 60(5):1162–1167
Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA (2001) Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Hum Mol Genet 10(12):1287–1298
Wu L, Hickson ID (2002) The Bloom’s syndrome helicase stimulates the activity of human topoisomerase IIIalpha. Nucleic Acids Res 30(22):4823–4829
Yang J, Bachrati CZ, Ou J, Hickson ID, Brown GW (2010) Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J Biol Chem 285(28):21426–21436
Wu L, Hickson ID (2003) The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature 426(6968):870–874
Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW (1983) The double-strand-break repair model for recombination. Cell 33(1):25–35
Ip SC, Rass U, Blanco MG, Flynn HR, Skehel JM, West SC (2008) Identification of Holliday junction resolvases from humans and yeast. Nature 456(7220):357–361
Wechsler T, Newman S, West SC (2011) Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature 471(7340):642–646
Luo G, Santoro IM, McDaniel LD, Nishijima I, Mills M, Youssoufian H, Vogel H, Schultz RA, Bradley A (2000) Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet 26(4):424–429
LaRocque JR, Stark JM, Oh J, Bojilova E, Yusa K, Horie K, Takeda J, Jasin M (2011) Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells. Proc Natl Acad Sci USA 108(29):11971–11976
Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID (2006) BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci USA 103(11):4068–4073
Raynard S, Bussen W, Sung P (2006) A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem 281(20):13861–13864
Raynard S, Zhao W, Bussen W, Lu L, Ding YY, Busygina V, Meetei AR, Sung P (2008) Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent Holliday junction processing. J Biol Chem 283(23):15701–15708
Murzin AG (1993) Ob(oligonucleotide oligosaccharide binding)-Fold—common structural and functional solution for nonhomologous sequences. EMBO J 12(3):861–867
Xu D, Guo R, Sobeck A, Bachrati CZ, Yang J, Enomoto T, Brown GW, Hoatlin ME, Hickson ID, Wang W (2008) RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev 22(20):2843–2855
Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado-Cruzata L, Rothstein R, Freyer GA, Boone C, Brown GW (2005) RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J 24(11):2024–2033
Mullen JR, Nallaseth FS, Lan YQ, Slagle CE, Brill SJ (2005) Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol Cell Biol 25(11):4476–4487
Chen CF, Brill SJ (2007) Binding and activation of DNA topoisomerase III by the Rmi1 subunit. J Biol Chem 282(39):28971–28979
Singh TR, Ali AM, Busygina V, Raynard S, Fan Q, Du CH, Andreassen PR, Sung P, Meetei AR (2008) BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev 22(20):2856–2868
Wang F, Yang Y, Singh TR, Busygina V, Guo R, Wan K, Wang W, Sung P, Meetei AR, Lei M (2010) Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex. Structure 18(9):1159–1170
Hoadley KA, Xu D, Xue Y, Satyshur KA, Wang W, Keck JL (2010) Structure and cellular roles of the RMI core complex from the Bloom syndrome dissolvasome. Structure 18(9):1149–1158
Gravel S, Chapman JR, Magill C, Jackson SP (2008) DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev 22(20):2767–2772
Doherty KM, Sharma S, Uzdilla LA, Wilson TM, Cui S, Vindigni A, Brosh RM Jr (2005) RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J Biol Chem 280(30):28085–28094
Sharma S, Sommers JA, Driscoll HC, Uzdilla L, Wilson TM, Brosh RM Jr (2003) The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. J Biol Chem 278(26):23487–23496
Liao S, Toczylowski T, Yan H (2008) Identification of the Xenopus DNA2 protein as a major nuclease for the 5′–3′ strand-specific processing of DNA ends. Nucleic Acids Res 36(19):6091–6100
Mimitou EP, Symington LS (2008) Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 455(7214):770–774
Zhu Z, Chung WH, Shim EY, Lee SE, Ira G (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 134(6):981–994
Cejka P, Cannavo E, Polaczek P, Masuda-Sasa T, Pokharel S, Campbell JL, Kowalczykowski SC (2010) DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature 467(7311):112–116
Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, Ira G, Sung P (2010) Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature 467(7311):108–111
Gaymes TJ, North PS, Brady N, Hickson ID, Mufti GJ, Rassool FV (2002) Increased error-prone non homologous DNA end-joining–a proposed mechanism of chromosomal instability in Bloom’s syndrome. Oncogene 21(16):2525–2533
Symington LS, Gautier J (2011) Double-strand break end resection and repair pathway choice. Annu Rev Genet 45:247–271
Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, Jaulin C, Amor-Gueret M (2000) Cell cycle regulation of the endogenous wild type Bloom’s syndrome DNA helicase. Oncogene 19(23):2731–2738
Sanz MM, Proytcheva M, Ellis NA, Holloman WK, German J (2000) BLM, the Bloom’s syndrome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins. Cytogenet Cell Genet 91(1–4):217–223
Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J (2001) Regulation and localization of the Bloom syndrome protein in response to DNA damage. J Cell Biol 153(2):367–380
San Filippo J, Sung P, Klein H (2008) Mechanism of eukaryotic homologous recombination. Annu Rev Biochem 77:229–257
Bachrati CZ, Borts RH, Hickson ID (2006) Mobile D-loops are a preferred substrate for the Bloom’s syndrome helicase. Nucleic Acids Res 34(8):2269–2279
Bugreev DV, Yu X, Egelman EH, Mazin AV (2007) Novel pro- and anti-recombination activities of the Bloom’s syndrome helicase. Genes Dev 21(23):3085–3094
Bugreev DV, Mazina OM, Mazin AV (2009) Bloom syndrome helicase stimulates RAD51 DNA strand exchange activity through a novel mechanism. J Biol Chem 284(39):26349–26359
Kikuchi K, Abdel-Aziz HI, Taniguchi Y, Yamazoe M, Takeda S, Hirota K (2009) Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences. J Biol Chem 284(39):26360–26367
Hanada K, Ukita T, Kohno Y, Saito K, Kato J, Ikeda H (1997) RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli. Proc Natl Acad Sci USA 94(8):3860–3865
Hand R, German J (1975) A retarded rate of DNA chain growth in Bloom’s syndrome. Proc Natl Acad Sci USA 72(2):758–762
Ockey CH, Saffhill R (1986) Delayed DNA maturation, a possible cause of the elevated sister-chromatid exchange in Bloom’s syndrome. Carcinogenesis 7(1):53–57
Lonn U, Lonn S, Nylen U, Winblad G, German J (1990) An abnormal profile of DNA replication intermediates in Bloom’s syndrome. Cancer Res 50(11):3141–3145
Sengupta S, Linke SP, Pedeux R, Yang Q, Farnsworth J, Garfield SH, Valerie K, Shay JW, Ellis NA, Wasylyk B, Harris CC (2003) BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. EMBO J 22(5):1210–1222
Wu L (2007) Role of the BLM helicase in replication fork management. DNA Repair (Amst) 6(7):936–944
Petermann E, Helleday T (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol 11(10):683–687
Jones RM, Petermann E (2012) Replication fork dynamics and the DNA damage response. Biochem J 443(1):13–26
Karow JK, Constantinou A, Li JL, West SC, Hickson ID (2000) The Bloom’s syndrome gene product promotes branch migration of Holliday junctions. Proc Natl Acad Sci USA 97(12):6504–6508
Ralf C, Hickson ID, Wu L (2006) The Bloom’s syndrome helicase can promote the regression of a model replication fork. J Biol Chem 281(32):22839–22846
Machwe A, Xiao L, Groden J, Orren DK (2006) The Werner and Bloom syndrome proteins catalyze regression of a model replication fork. Biochemistry 45(47):13939–13946
Tuduri S, Tourriere H, Pasero P (2010) Defining replication origin efficiency using DNA fiber assays. Chromosome Res 18(1):91–102
Davies SL, North PS, Hickson ID (2007) Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat Struct Mol Biol 14(7):677–679
Rao VA, Conti C, Guirouilh-Barbat J, Nakamura A, Miao ZH, Davies SL, Sacca B, Hickson ID, Bensimon A, Pommier Y (2007) Endogenous gamma-H2AX-ATM-Chk2 checkpoint activation in Bloom’s syndrome helicase deficient cells is related to DNA replication arrested forks. Mol Cancer Res 5(7):713–724
Yang J, O’Donnell L, Durocher D, Brown GW (2012) RMI1 promotes DNA replication fork progression and recovery from replication fork stress. Mol Cell Biol 32(15):3054–3064
Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W (2003) A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol Cell Biol 23(10):3417–3426
Deans AJ, West SC (2009) FANCM connects the genome instability disorders Bloom’s syndrome and Fanconi anemia. Mol Cell 36(6):943–953
Moldovan GL, D’Andrea AD (2009) How the Fanconi anemia pathway guards the genome. Annu Rev Genet 43:223–249
Kee Y, D’Andrea AD (2010) Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev 24(16):1680–1694
Niedernhofer LJ, Lalai AS, Hoeijmakers JH (2005) Fanconi anemia (cross)linked to DNA repair. Cell 123(7):1191–1198
Kim H, D’Andrea AD (2012) Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway. Genes Dev 26(13):1393–1408
Nakanishi K, Cavallo F, Perrouault L, Giovannangeli C, Moynahan ME, Barchi M, Brunet E, Jasin M (2011) Homology-directed Fanconi anemia pathway cross-link repair is dependent on DNA replication. Nat Struct Mol Biol 18(4):500–503
Knipscheer P, Raschle M, Smogorzewska A, Enoiu M, Ho TV, Scharer OD, Elledge SJ, Walter JC (2009) The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science 326(5960):1698–1701
Wang W (2007) Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 8(10):735–748
Pichierri P, Franchitto A, Rosselli F (2004) BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. EMBO J 23(15):3154–3163
Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W (2005) A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet 37(9):958–963
Komori K, Fujikane R, Shinagawa H, Ishino Y (2002) Novel endonuclease in Archaea cleaving DNA with various branched structure. Genes Genet Syst 77(4):227–241
Scheller J, Schurer A, Rudolph C, Hettwer S, Kramer W (2000) MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage. Genetics 155(3):1069–1081
Sun W, Nandi S, Osman F, Ahn JS, Jakovleska J, Lorenz A, Whitby MC (2008) The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair. Mol Cell 32(1):118–128
Yan Z, Delannoy M, Ling C, Daee D, Osman F, Muniandy PA, Shen X, Oostra AB, Du H, Steltenpool J, Lin T, Schuster B, Decaillet C, Stasiak A, Stasiak AZ, Stone S, Hoatlin ME, Schindler D, Woodcock CL, Joenje H, Sen R, de Winter JP, Li L, Seidman MM, Whitby MC, Myung K, Constantinou A, Wang W (2010) A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell 37(6):865–878
Singh TR, Saro D, Ali AM, Zheng XF, Du CH, Killen MW, Sachpatzidis A, Wahengbam K, Pierce AJ, Xiong Y, Sung P, Meetei AR (2010) MHF1–MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM. Mol Cell 37(6):879–886
Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei AR, el Laghmani H, Joenje H, McDonald N, de Winter JP, Wang W, West SC (2007) Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol Cell 25(3):331–343
Rosado IV, Niedzwiedz W, Alpi AF, Patel KJ (2009) The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair. Nucleic Acids Res 37(13):4360–4370
Niedzwiedz W, Mosedale G, Johnson M, Ong CY, Pace P, Patel KJ (2004) The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair. Mol Cell 15(4):607–620
Hirano S, Yamamoto K, Ishiai M, Yamazoe M, Seki M, Matsushita N, Ohzeki M, Yamashita YM, Arakawa H, Buerstedde JM, Enomoto T, Takeda S, Thompson LH, Takata M (2005) Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. EMBO J 24(2):418–427
Bridge WL, Vandenberg CJ, Franklin RJ, Hiom K (2005) The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nat Genet 37(9):953–957
Xue Y, Li Y, Guo R, Ling C, Wang W (2008) FANCM of the Fanconi anemia core complex is required for both monoubiquitination and DNA repair. Hum Mol Genet 17(11):1641–1652
Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR (2009) Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood 114(1):174–180
Gari K, Decaillet C, Delannoy M, Wu L, Constantinou A (2008) Remodeling of DNA replication structures by the branch point translocase FANCM. Proc Natl Acad Sci USA 105(42):16107–16112
Collis SJ, Ciccia A, Deans AJ, Horejsi Z, Martin JS, Maslen SL, Skehel JM, Elledge SJ, West SC, Boulton SJ (2008) FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Mol Cell 32(3):313–324
Luke-Glaser S, Luke B, Grossi S, Constantinou A (2010) FANCM regulates DNA chain elongation and is stabilized by S-phase checkpoint signalling. EMBO J 29(4):795–805
Schwab RA, Blackford AN, Niedzwiedz W (2010) ATR activation and replication fork restart are defective in FANCM-deficient cells. EMBO J 29(4):806–818
Blackford AN, Schwab RA, Nieminuszczy J, Deans AJ, West SC, Niedzwiedz W (2012) The DNA translocase activity of FANCM protects stalled replication forks. Hum Mol Genet 21(9):2005–2016
Hoadley KA, Xue Y, Ling C, Takata M, Wang W, Keck JL (2012) Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome. Proc Natl Acad Sci USA 109(12):4437–4442
Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM (2004) The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci USA 101(8):2357–2362
Suhasini AN, Brosh RM Jr (2012) Fanconi anemia and Bloom’s syndrome crosstalk through FANCJ-BLM helicase interaction. Trends Genet 28(1):7–13
Wu Y, Shin-ya K, Brosh RM Jr (2008) FANCJ helicase defective in Fanconi anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability. Mol Cell Biol 28(12):4116–4128
London TB, Barber LJ, Mosedale G, Kelly GP, Balasubramanian S, Hickson ID, Boulton SJ, Hiom K (2008) FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. J Biol Chem 283(52):36132–36139
Sarkies P, Murat P, Phillips LG, Patel KJ, Balasubramanian S, Sale JE (2012) FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA. Nucleic Acids Res 40(4):1485–1498
Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15(17):2177–2196
Syljuasen RG, Sorensen CS, Hansen LT, Fugger K, Lundin C, Johansson F, Helleday T, Sehested M, Lukas J, Bartek J (2005) Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol 25(9):3553–3562
O’Driscoll M, Jeggo PA (2006) The role of double-strand break repair—insights from human genetics. Nat Rev Genet 7(1):45–54
Rao VA, Fan AM, Meng L, Doe CF, North PS, Hickson ID, Pommier Y (2005) Phosphorylation of BLM, dissociation from topoisomerase IIIalpha, and colocalization with gamma-H2AX after topoisomerase I-induced replication damage. Mol Cell Biol 25(20):8925–8937
Ababou M, Dutertre S, Lecluse Y, Onclercq R, Chatton B, Amor-Gueret M (2000) ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation. Oncogene 19(52):5955–5963
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D’Andrea AD (2002) Convergence of the Fanconi anemia and ataxia telangiectasia signaling pathways. Cell 109(4):459–472
Pichierri P, Rosselli F (2004) The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. EMBO J 23(5):1178–1187
Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER 3rd, Hurov KE, Luo J, Ballif BA, Gygi SP, Hofmann K, D’Andrea AD, Elledge SJ (2007) Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell 129(2):289–301
Ishiai M, Kitao H, Smogorzewska A, Tomida J, Kinomura A, Uchida E, Saberi A, Kinoshita E, Kinoshita-Kikuta E, Koike T, Tashiro S, Elledge SJ, Takata M (2008) FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Nat Struct Mol Biol 15(11):1138–1146
Collins NB, Wilson JB, Bush T, Thomashevski A, Roberts KJ, Jones NJ, Kupfer GM (2009) ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function. Blood 113(10):2181–2190
Wang X, Kennedy RD, Ray K, Stuckert P, Ellenberger T, D’Andrea AD (2007) Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol 27(8):3098–3108
Wang Y, Leung JW, Jiang Y, Lowery MG, Do H, Vasquez KM, Chen J, Wang W, Li L (2013) FANCM and FAAP24 maintain genome stability via cooperative as well as unique functions. Mol Cell 49(5):997–1009
Gong Z, Kim JE, Leung CC, Glover JN, Chen J (2010) BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Mol Cell 37(3):438–446
Baumann C, Korner R, Hofmann K, Nigg EA (2007) PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint. Cell 128(1):101–114
Chan KL, North PS, Hickson ID (2007) BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J 26(14):3397–3409
Chan KL, Hickson ID (2011) New insights into the formation and resolution of ultra-fine anaphase bridges. Semin Cell Dev Biol 22(8):906–912
Wang LH, Schwarzbraun T, Speicher MR, Nigg EA (2008) Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation. Chromosoma 117(2):123–135
Rouzeau S, Cordelieres FP, Buhagiar-Labarchede G, Hurbain I, Onclercq-Delic R, Gemble S, Magnaghi-Jaulin L, Jaulin C, Amor-Gueret M (2012) Bloom’s syndrome and PICH helicases cooperate with topoisomerase IIalpha in centromere disjunction before anaphase. PLoS ONE 7(4):e33905
Spence JM, Phua HH, Mills W, Carpenter AJ, Porter AC, Farr CJ (2007) Depletion of topoisomerase IIalpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads. J Cell Sci 120(Pt 22):3952–3964
Russell B, Bhattacharyya S, Keirsey J, Sandy A, Grierson P, Perchiniak E, Kavecansky J, Acharya S, Groden J (2011) Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha. Cancer Res 71(2):561–571
Chan KL, Palmai-Pallag T, Ying S, Hickson ID (2009) Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol 11(6):753–760
Naim V, Rosselli F (2009) The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities. Nat Cell Biol 11(6):761–768
Letessier A, Millot GA, Koundrioukoff S, Lachages AM, Vogt N, Hansen RS, Malfoy B, Brison O, Debatisse M (2011) Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature 470(7332):120–123
Ozeri-Galai E, Lebofsky R, Rahat A, Bester AC, Bensimon A, Kerem B (2011) Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell 43(1):122–131
Vinciguerra P, Godinho SA, Parmar K, Pellman D, D’Andrea AD (2010) Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells. J Clin Invest 120(11):3834–3842
Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B, Pedersen RS, Grofte M, Chan KL, Hickson ID, Bartek J, Lukas J (2011) 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat Cell Biol 13(3):243–253
Harrigan JA, Belotserkovskaya R, Coates J, Dimitrova DS, Polo SE, Bradshaw CR, Fraser P, Jackson SP (2011) Replication stress induces 53BP1-containing OPT domains in G1 cells. J Cell Biol 193(1):97–108
Adamo A, Collis SJ, Adelman CA, Silva N, Horejsi Z, Ward JD, Martinez-Perez E, Boulton SJ, La Volpe A (2010) Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39(1):25–35
Pace P, Mosedale G, Hodskinson MR, Rosado IV, Sivasubramaniam M, Patel KJ (2010) Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway. Science 329(5988):219–223
Karanja KK, Cox SW, Duxin JP, Stewart SA, Campbell JL (2012) DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network. Cell Cycle 11(21):3983–3996
Nguyen GH, Dexheimer TS, Rosenthal AS, Chu WK, Singh DK, Mosedale G, Bachrati CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC, Jadhav A, Gileadi O, Maloney DJ, Simeonov A, Hickson ID (2013) A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem Biol 20(1):55–62
Delano WL (2002) The PyMol molecular graphics system. DeLano Scientific, San Carolos
Li W, Wang JC (1998) Mammalian DNA topoisomerase IIIalpha is essential in early embryogenesis. Proc Natl Acad Sci USA 95(3):1010–1013
Seki M, Nakagawa T, Seki T, Kato G, Tada S, Takahashi Y, Yoshimura A, Kobayashi T, Aoki A, Otsuki M, Habermann FA, Tanabe H, Ishii Y, Enomoto T (2006) Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids. Mol Cell Biol 26(16):6299–6307
Wang W, Seki M, Narita Y, Sonoda E, Takeda S, Yamada K, Masuko T, Katada T, Enomoto T (2000) Possible association of BLM in decreasing DNA double strand breaks during DNA replication. EMBO J 19(13):3428–3435
Acknowledgments
We apologize to all authors whose work we could not cite due to space limitations. Work in our laboratory was funded by a grant from the National Institutes of Health (GM068061) and K.A.M. was supported in part by a National Institutes of Health training grant in Molecular Biosciences (GM07215).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Manthei, K.A., Keck, J.L. The BLM dissolvasome in DNA replication and repair. Cell. Mol. Life Sci. 70, 4067–4084 (2013). https://doi.org/10.1007/s00018-013-1325-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-013-1325-1