DNA Helicases Associated with Genetic Instability, Cancer, and Aging

  • Avvaru N. Suhasini
  • Robert M. BroshJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 973)


DNA helicases have essential roles in the maintenance of genomic ­stability. They have achieved even greater prominence with the discovery that mutations in human helicase genes are responsible for a variety of genetic disorders and are associated with tumorigenesis. A number of missense mutations in human helicase genes are linked to chromosomal instability diseases characterized by age-related disease or associated with cancer, providing incentive for the characterization of molecular defects underlying aberrant cellular phenotypes. In this chapter, we discuss some examples of clinically relevant missense mutations in various human DNA helicases, particularly those of the Iron-Sulfur cluster and RecQ families. Clinically relevant mutations in the XPD helicase can lead to Xeroderma pigmentosum, Cockayne’s syndrome, Trichothiodystrophy, or COFS syndrome. FANCJ mutations are associated with Fanconi anemia or breast cancer. Mutations of the Fe-S helicase ChlR1 (DDX11) are linked to Warsaw Breakage syndrome. Mutations in the RecQ helicases BLM and WRN are linked to the cancer-prone disorder Bloom’s syndrome and premature aging condition Werner syndrome, respectively. RECQL4 mutations can lead to Rothmund-Thomson syndrome, Baller-Gerold syndrome, or RAPADILINO. Mutations in the Twinkle mitochondrial helicase are responsible for several neuromuscular degenerative disorders. We will discuss some insights gained from biochemical and genetic studies of helicase variants, and highlight some hot areas of helicase research based on recent developments.


Nucleotide Excision Repair Fanconi Anemia Xeroderma Pigmentosum Helicase Activity Werner Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the Fanconi Anemia Research Fund (RMB). We apologize to helicase researchers whose work was not cited due to space limitations.


  1. 1.
    Lohman TM, Tomko EJ, Wu CG. Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nat Rev Mol Cell Biol. 2008;9:391–401.PubMedCrossRefGoogle Scholar
  2. 2.
    Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Annu Rev Biochem. 2007;76:23–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Brosh Jr RM, Bohr VA. Human premature aging, DNA repair and RecQ helicases. Nucleic Acids Res. 2007;35:7527–44.PubMedCrossRefGoogle Scholar
  4. 4.
    Lohman TM, Bjornson KP. Mechanisms of helicase-catalyzed DNA unwinding. Annu Rev Biochem. 1996;65:169–214.PubMedCrossRefGoogle Scholar
  5. 5.
    Patel SS, Donmez I. Mechanisms of helicases. J Biol Chem. 2006;281:18265–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Pyle AM. Translocation and unwinding mechanisms of RNA and DNA helicases. Annu Rev Biophys. 2008;37:317–36.PubMedCrossRefGoogle Scholar
  7. 7.
    Bernstein KA, Gangloff S, Rothstein R. The RecQ DNA helicases in DNA repair. Annu Rev Genet. 2010;44:393–417.PubMedCrossRefGoogle Scholar
  8. 8.
    Dillingham MS, Superfamily I. helicases as modular components of DNA-processing machines. Biochem Soc Trans. 2011;39:413–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Singh DK, Ghosh AK, Croteau DL, Bohr VA. RecQ helicases in DNA double strand break repair and telomere maintenance. Mutat Res. 2012;736:15–24.PubMedCrossRefGoogle Scholar
  10. 10.
    Wu Y, Suhasini AN, Brosh RM. Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins. Cell Mol Life Sci. 2009;66:1209–22.PubMedCrossRefGoogle Scholar
  11. 11.
    White MF. Structure, function and evolution of the XPD family of iron-sulfur-containing 5′–>3′ DNA helicases. Biochem Soc Trans. 2009;37:547–51.PubMedCrossRefGoogle Scholar
  12. 12.
    White MF, Dillingham MS. Iron-sulphur clusters in nucleic acid processing enzymes. Curr Opin Struct Biol. 2012;22:94–100.PubMedCrossRefGoogle Scholar
  13. 13.
    Digiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012;132:785–96.PubMedCrossRefGoogle Scholar
  14. 14.
    Egly JM, Coin F. A history of TFIIH: two decades of molecular biology on a pivotal transcription/repair factor. DNA Repair (Amst). 2011;10:714–21.CrossRefGoogle Scholar
  15. 15.
    Oksenych V, Coin F. The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell Cycle. 2010;9:90–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Crossan GP, Patel KJ. The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA. J Pathol. 2012;226:326–37.PubMedCrossRefGoogle Scholar
  17. 17.
    Deans AJ, West SC. DNA interstrand crosslink repair and cancer. Nat Rev Cancer. 2011;11:467–80.PubMedCrossRefGoogle Scholar
  18. 18.
    Cantor SB, Guillemette S. Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1. Future Oncol. 2011;7:253–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Cantor SB, Bell DW, Ganesan S, et al. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell. 2001;105:149–60.PubMedCrossRefGoogle Scholar
  20. 20.
    London TB, Barber LJ, Mosedale G, et al. FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. J Biol Chem. 2008;283:36132–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Wu Y, Shin-Ya K, Brosh Jr RM. FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability. Mol Cell Biol. 2008;28:4116–28.PubMedCrossRefGoogle Scholar
  22. 22.
    van der LP, Chrzanowska KH, Godthelp BC, et al. Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. Am J Hum Genet. 2010;86:262–6.CrossRefGoogle Scholar
  23. 23.
    Skibbens RV. Chl1p, a DNA helicase-like protein in budding yeast, functions in sister-chromatid cohesion. Genetics. 2004;166:33–42.PubMedCrossRefGoogle Scholar
  24. 24.
    Inoue A, Li T, Roby SK, et al. Loss of ChlR1 helicase in mouse causes lethality due to the accumulation of aneuploid cells generated by cohesion defects and placental malformation. Cell Cycle. 2007;6:1646–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Parish JL, Rosa J, Wang X, Lahti JM, Doxsey SJ, Androphy EJ. The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells. J Cell Sci. 2006;119:4857–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Inoue A, Hyle J, Lechner MS, Lahti JM. Mammalian ChlR1 has a role in heterochromatin organization. Exp Cell Res. 2011;317:2522–35.PubMedCrossRefGoogle Scholar
  27. 27.
    Ellis NA, Groden J, Ye TZ, et al. The Bloom’s syndrome gene product is homologous to RecQ helicases. Cell. 1995;83:655–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Chaganti RS, Schonberg S, German J. A manyfold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes. Proc Natl Acad Sci USA. 1974;71:4508–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Bachrati CZ, Hickson ID. Dissolution of double Holliday junctions by the concerted action of BLM and topoisomerase IIIalpha. Methods Mol Biol. 2009;582:91–102.PubMedCrossRefGoogle Scholar
  30. 30.
    Wu L, Hickson ID. The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature. 2003;426:870–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Chu WK, Hanada K, Kanaar R, Hickson ID. BLM has early and late functions in homologous recombination repair in mouse embryonic stem cells. Oncogene. 2010;29:4705–14.PubMedCrossRefGoogle Scholar
  32. 32.
    Nimonkar AV, Genschel J, Kinoshita E, et al. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011;25:350–62.PubMedCrossRefGoogle Scholar
  33. 33.
    Chan KL, Palmai-Pallag T, Ying S, Hickson ID. Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol. 2009;11:753–60.PubMedCrossRefGoogle Scholar
  34. 34.
    Monnat Jr RJ. Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology. Semin Cancer Biol. 2010;20:329–39.PubMedCrossRefGoogle Scholar
  35. 35.
    Rossi ML, Ghosh AK, Bohr VA. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair (Amst). 2010;9:331–44.CrossRefGoogle Scholar
  36. 36.
    Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome. Orphanet J Rare Dis. 2010;5:2.PubMedCrossRefGoogle Scholar
  37. 37.
    Van Maldergem L, Siitonen HA, Jalkh N, et al. Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene. J Med Genet. 2006;43:148–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Singh DK, Karmakar P, Aamann M, et al. The involvement of human RECQL4 in DNA double-strand break repair. Aging Cell. 2010;9:358–71.PubMedCrossRefGoogle Scholar
  39. 39.
    Ghosh AK, Rossi ML, Singh DK, et al. RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance. J Biol Chem. 2012;287:196–209.PubMedCrossRefGoogle Scholar
  40. 40.
    Croteau DL, Rossi ML, Canugovi C, et al. RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity. Aging Cell. 2012;11(3):456–66.PubMedCrossRefGoogle Scholar
  41. 41.
    De S, Kumari J, Mudgal R, et al. RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress. J Cell Sci. 2012;125:2509–22.PubMedCrossRefGoogle Scholar
  42. 42.
    Sharma S, Doherty KM, Brosh Jr RM. Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability. Biochem J. 2006;398:319–37.PubMedCrossRefGoogle Scholar
  43. 43.
    Sharma S, Stumpo DJ, Balajee AS, et al. RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability. Mol Cell Biol. 2007;27:1784–94.PubMedCrossRefGoogle Scholar
  44. 44.
    Sharma S, Brosh Jr RM. Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges. PLoS One. 2007;2:e1297.PubMedCrossRefGoogle Scholar
  45. 45.
    Thangavel S, Mendoza-Maldonado R, Tissino E, et al. The human RECQ1 and RECQ4 ­helicases play distinct roles in DNA replication initiation. Mol Cell Biol. 2010;30:1382–96.PubMedCrossRefGoogle Scholar
  46. 46.
    Aygun O, Svejstrup J, Liu Y. A RECQ5-RNA polymerase II association identified by targeted proteomic analysis of human chromatin. Proc Natl Acad Sci USA. 2008;105:8580–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Kanagaraj R, Huehn D, MacKellar A, et al. RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription. Nucleic Acids Res. 2010;38:8131–40.PubMedCrossRefGoogle Scholar
  48. 48.
    Ramamoorthy M, Tadokoro T, Rybanska I, et al. RECQL5 cooperates with topoisomerase II alpha in DNA decatenation and cell cycle progression. Nucleic Acids Res. 2012;40:1621–35.PubMedCrossRefGoogle Scholar
  49. 49.
    Copeland WC. Defects in mitochondrial DNA replication and human disease. Crit Rev Biochem Mol Biol. 2012;47:64–74.PubMedCrossRefGoogle Scholar
  50. 50.
    Korhonen JA, Gaspari M, Falkenberg M. TWINKLE Has 5′ -> 3′ DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. J Biol Chem. 2003;278:48627–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Sen D, Nandakumar D, Tang GQ, Patel SS. The human mitochondrial DNA helicase TWINKLE is both an unwinding and an annealing helicase. J Biol Chem. 2012;287(18):14545–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Ziebarth TD, Gonzalez-Soltero R, Makowska-Grzyska MM, Nunez-Ramirez R, Carazo JM, Kaguni LS. Dynamic effects of cofactors and DNA on the oligomeric state of human ­mitochondrial DNA helicase. J Biol Chem. 2010;285:14639–47.PubMedCrossRefGoogle Scholar
  53. 53.
    Dubaele S, De Proietti SL, Bienstock RJ, et al. Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients. Mol Cell. 2003;11:1635–46.PubMedCrossRefGoogle Scholar
  54. 54.
    Lehmann AR. XPD structure reveals its secrets. DNA Repair (Amst). 2008;7:1912–5.CrossRefGoogle Scholar
  55. 55.
    Coin F, Oksenych V, Egly JM. Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair. Mol Cell. 2007;26:245–56.PubMedCrossRefGoogle Scholar
  56. 56.
    Graham Jr JM, Nyane-Yeboa K, Raams A, et al. Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. Am J Hum Genet. 2001;69:291–300.PubMedCrossRefGoogle Scholar
  57. 57.
    Peng M, Litman R, Xie J, Sharma S, Brosh Jr RM, Cantor SB. The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells. EMBO J. 2007;26:3238–49.PubMedCrossRefGoogle Scholar
  58. 58.
    Levran O, Attwooll C, Henry RT, et al. The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet. 2005;37:931–3.PubMedCrossRefGoogle Scholar
  59. 59.
    Wu Y, Sommers JA, Suhasini AN, et al. Fanconi anemia Group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes. Blood. 2010;116:3780–91.PubMedCrossRefGoogle Scholar
  60. 60.
    Yu X, Chini CC, He M, Mer G, Chen J. The BRCT domain is a phospho-protein binding domain. Science. 2003;302:639–42.PubMedCrossRefGoogle Scholar
  61. 61.
    Xie J, Litman R, Wang S, et al. Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Oncogene. 2010;29:2499–508.PubMedCrossRefGoogle Scholar
  62. 62.
    Farina A, Shin JH, Kim DH, et al. Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1. J Biol Chem. 2008;283:20925–36.PubMedCrossRefGoogle Scholar
  63. 63.
    Hirota Y, Lahti JM. Characterization of the enzymatic activity of hChlR1, a novel human DNA helicase. Nucleic Acids Res. 2000;28:917–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Wu Y, Sommers JA, Khan I, De Winter JP, Brosh Jr RM. Biochemical characterization of warsaw breakage syndrome helicase. J Biol Chem. 2012;287:1007–21.PubMedCrossRefGoogle Scholar
  65. 65.
    German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Hum Mutat. 2007;28:743–53.PubMedCrossRefGoogle Scholar
  66. 66.
    Neff NF, Ellis NA, Ye TZ, et al. The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells. Mol Biol Cell. 1999;10:665–76.PubMedGoogle Scholar
  67. 67.
    Bahr A, De Graeve F, Kedinger C, Chatton B. Point mutations causing Bloom’s syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene. 1998;17:2565–71.PubMedCrossRefGoogle Scholar
  68. 68.
    Guo RB, Rigolet P, Zargarian L, Fermandjian S, Xi XG. Structural and functional characterizations reveal the importance of a zinc binding domain in Bloom’s syndrome helicase. Nucleic Acids Res. 2005;33(10):3109–24.PubMedCrossRefGoogle Scholar
  69. 69.
    Guo RB, Rigolet P, Ren H, et al. Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein. Nucleic Acids Res. 2007;35:6297–310.PubMedCrossRefGoogle Scholar
  70. 70.
    Wang XW, Tseng A, Ellis NA, et al. Functional interaction of p53 and BLM DNA helicase in apoptosis. J Biol Chem. 2001;276:32948–55.PubMedCrossRefGoogle Scholar
  71. 71.
    Yu CE, Oshima J, Fu YH, et al. Positional cloning of the Werner’s syndrome gene. Science. 1996;272:258–62.PubMedCrossRefGoogle Scholar
  72. 72.
    Suzuki T, Shiratori M, Furuichi Y, Matsumoto T. Diverged nuclear localization of Werner helicase in human and mouse cells. Oncogene. 2001;20:2551–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Friedrich K, Lee L, Leistritz DF, et al. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations. Hum Genet. 2010;128:103–11.PubMedCrossRefGoogle Scholar
  74. 74.
    Huang S, Lee L, Hanson NB, et al. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006;27:558–67.PubMedCrossRefGoogle Scholar
  75. 75.
    Uhrhammer NA, Lafarge L, Dos SL, et al. Werner syndrome and mutations of the WRN and LMNA genes in France. Hum Mutat. 2006;27:718–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Swanson C, Saintigny Y, Emond MJ, Monnat Jr RJ. The Werner syndrome protein has separable recombination and survival functions. DNA Repair (Amst). 2004;3:475–82.CrossRefGoogle Scholar
  77. 77.
    Chen L, Huang S, Lee L, et al. WRN, the protein deficient in Werner syndrome, plays a critical structural role in optimizing DNA repair. Aging Cell. 2003;2:191–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Opresko PL, Otterlei M, Graakjaer J, et al. The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol Cell. 2004;14:763–74.PubMedCrossRefGoogle Scholar
  79. 79.
    Oh KS, Khan SG, Jaspers NG, et al. Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Hum Mutat. 2006;27:1092–103.PubMedCrossRefGoogle Scholar
  80. 80.
    Weeda G, Eveno E, Donker I, et al. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. Am J Hum Genet. 1997;60:320–9.PubMedGoogle Scholar
  81. 81.
    Riou L, Zeng L, Chevallier-Lagente O, et al. The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne’s syndrome or trichothiodystrophy cellular phenotypes. Hum Mol Genet. 1999;8:1125–33.PubMedCrossRefGoogle Scholar
  82. 82.
    Goffart S, Cooper HM, Tyynismaa H, Wanrooij S, Suomalainen A, Spelbrink JN. Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Hum Mol Genet. 2009;18:328–40.PubMedCrossRefGoogle Scholar
  83. 83.
    Tyynismaa H, Mjosund KP, Wanrooij S, et al. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc Natl Acad Sci USA. 2005;102:17687–92.PubMedCrossRefGoogle Scholar
  84. 84.
    Wanrooij S, Goffart S, Pohjoismaki JL, Yasukawa T, Spelbrink JN. Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic Acids Res. 2007;35:3238–51.PubMedCrossRefGoogle Scholar
  85. 85.
    Longley MJ, Humble MM, Sharief FS, Copeland WC. Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity. J Biol Chem. 2010;285:29690–702.PubMedCrossRefGoogle Scholar
  86. 86.
    Boal AK, Genereux JC, Sontz PA, Gralnick JA, Newman DK, Barton JK. Redox signaling between DNA repair proteins for efficient lesion detection. Proc Natl Acad Sci USA. 2009;106:15237–42.PubMedCrossRefGoogle Scholar
  87. 87.
    Romano CA, Sontz PA, Barton JK. Mutants of the base excision repair glycosylase, endonuclease III: DNA charge transport as a first step in lesion detection. Biochemistry. 2011;50:6133–45.PubMedCrossRefGoogle Scholar
  88. 88.
    Merino EJ, Boal AK, Barton JK. Biological contexts for DNA charge transport chemistry. Curr Opin Chem Biol. 2008;12:229–37.PubMedCrossRefGoogle Scholar
  89. 89.
    Sontz PA, Mui TP, Fuss JO, Tainer JA, Barton JK. DNA charge transport as a first step in coordinating the detection of lesions by repair proteins. Proc Natl Acad Sci USA. 2012;109:1856–61.PubMedCrossRefGoogle Scholar
  90. 90.
    Constantinou A. Rescue of replication failure by Fanconi anaemia proteins. Chromosoma. 2012;121:21–36.PubMedCrossRefGoogle Scholar
  91. 91.
    Hakem R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 2008;27:589–605.PubMedCrossRefGoogle Scholar
  92. 92.
    Lagerwerf S, Vrouwe MG, Overmeer RM, Fousteri MI, Mullenders LH. DNA damage response and transcription. DNA Repair (Amst). 2011;10:743–50.CrossRefGoogle Scholar
  93. 93.
    Wilson III DM, Seidman MM. A novel link to base excision repair? Trends Biochem Sci. 2010;35:247–52.PubMedCrossRefGoogle Scholar
  94. 94.
    Gravel S, Chapman JR, Magill C, Jackson SP. DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev. 2008;22:2767–72.PubMedCrossRefGoogle Scholar
  95. 95.
    Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci USA. 2008;105:16906–11.PubMedCrossRefGoogle Scholar
  96. 96.
    Suhasini AN, Rawtani NA, Wu Y, et al. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom’s syndrome. EMBO J. 2011;30:692–705.PubMedCrossRefGoogle Scholar
  97. 97.
    Litman R, Peng M, Jin Z, et al. BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell. 2005;8:255–65.PubMedCrossRefGoogle Scholar
  98. 98.
    Suhasini AN, Brosh Jr RM. Fanconi anemia and Bloom’s syndrome crosstalk through FANCJ-BLM helicase interaction. Trends Genet. 2012;28:7–13.PubMedCrossRefGoogle Scholar
  99. 99.
    Rudolf J, Makrantoni V, Ingledew WJ, Stark MJ, White MF. The DNA repair helicases XPD and FancJ have essential Iron-Sulfur domains. Mol Cell. 2006;23:801–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Fan L, Fuss JO, Cheng QJ, et al. XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. Cell. 2008;133:789–800.PubMedCrossRefGoogle Scholar
  101. 101.
    Liu H, Rudolf J, Johnson KA, et al. Structure of the DNA repair helicase XPD. Cell. 2008;133:801–12.PubMedCrossRefGoogle Scholar
  102. 102.
    Wolski SC, Kuper J, Hanzelmann P, et al. Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biol. 2008;6:e149.PubMedCrossRefGoogle Scholar
  103. 103.
    Pugh RA, Honda M, Leesley H, et al. The iron-containing domain is essential in Rad3 helicases for coupling of ATP hydrolysis to DNA translocation and for targeting the helicase to the single-stranded DNA-double-stranded DNA junction. J Biol Chem. 2008;283:1732–43.PubMedCrossRefGoogle Scholar
  104. 104.
    Kuper J, Wolski SC, Michels G, Kisker C. Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation. EMBO J. 2011;31:494–502.PubMedCrossRefGoogle Scholar
  105. 105.
    Pugh RA, Wu CG, Spies M. Regulation of translocation polarity by helicase domain 1 in SF2B helicases. EMBO J. 2011;31:503–14.PubMedCrossRefGoogle Scholar
  106. 106.
    Wu Y, Brosh Jr RM. DNA helicase and helicase-nuclease enzymes with a conserved iron-sulfur cluster. Nucleic Acids Res. 2012;40(10):4247–60.PubMedCrossRefGoogle Scholar
  107. 107.
    Aggarwal M, Brosh Jr RM. Hitting the bull’s eye: novel directed cancer therapy through helicase-targeted synthetic lethality. J Cell Biochem. 2009;106:758–63.PubMedCrossRefGoogle Scholar
  108. 108.
    Aggarwal M, Sommers JA, Shoemaker RH, Brosh Jr RM. Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proc Natl Acad Sci USA. 2011;108:1525–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of HealthNIH Biomedical Research CenterBaltimoreUSA

Personalised recommendations