REFERENCES
2. Croteau DL, Popuri V, Opresko PL, Bohr VA. Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem 2014;83:519-52.
3. Oshima J, Sidorova JM, Monnat RJ Jr. Werner syndrome: clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev 2017;33:105-14.
4. Opresko PL, Cheng WH, von Kobbe C, Harrigan JA, Bohr VA. Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 2003;24:791-802.
5. Kitano K, Yoshihara N, Hakoshima T. Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. J Biol Chem 2007;282:2717-28.
6. Lan L, Nakajima S, Komatsu K, et al. Accumulation of Werner protein at DNA double-strand breaks in human cells. J Cell Sci 2005;118:4153-62.
7. Perry JJ, Yannone SM, Holden LG, et al. WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nat Struct Mol Biol 2006;13:414-22.
8. Sidorova JM, Li N, Folch A, Monnat RJ Jr. The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest. Cell Cycle 2008;7:796-807.
9. Bugreev DV, Rossi MJ, Mazin AV. Cooperation of RAD51 and RAD54 in regression of a model replication fork. Nucleic Acids Res 2011;39:2153-64.
10. Constantinou A, Tarsounas M, Karow J K, et al. Werner’s syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep 2000;1:80-4.
11. Li K, Casta A, Wang R, et al. Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation. J Biol Chem 2008;283:7590-8.
12. Kahyo T, Mostoslavsky R, Goto M, Setou M. Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein. FEBS Lett 2008;582:2479-83.
13. Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 2011;12:90-103.
14. Hashimoto Y, Ray Chaudhuri A, Lopes M, Costanzo V. Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Nat Struct Mol Biol 2010;17:1305-11.
15. Lemaçon D, Jackson J, Quinet A, et al. MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nat Commun 2017;8:860.
16. Datta A, Biswas K, Sommers JA, et al. WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells. Nat Commun 2021;12:6561.
17. Sidorova J. A game of substrates: replication fork remodeling and its roles in genome stability and chemo-resistance. Cell Stress 2017;1:115-33.
18. Berti M, Ray Chaudhuri A, Thangavel S, et al. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat Struct Mol Biol 2013;20:347-54.
19. Iannascoli C, Palermo V, Murfuni I, Franchitto A, Pichierri P. The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1-dependent degradation. Nucleic Acids Res 2015;43:9788-803.
20. Su F, Mukherjee S, Yang Y, et al. Nonenzymatic role for WRN in preserving nascent DNA strands after replication stress. Cell Rep 2014;9:1387-401.
21. Newman JA, Gileadi O. RecQ helicases in DNA repair and cancer targets. Essays Biochem 2020;64:819-30.
22. Karmakar P, Snowden CM, Ramsden DA, Bohr VA. Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus. Nucleic Acids Res 2002;30:3583-91.
23. Grundy GJ, Rulten SL, Arribas-Bosacoma R, et al. The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins. Nat Commun 2016;7:11242.
24. Kusumoto-Matsuo R, Ghosh D, Karmakar P, May A, Ramsden D, Bohr VA. Serines 440 and 467 in the Werner syndrome protein are phosphorylated by DNA-PK and affects its dynamics in response to DNA double strand breaks. Aging (Albany NY) 2014;6:70-81.
25. Brosh RM Jr, Bohr VA. Human premature aging, DNA repair and RecQ helicases. Nucleic Acids Res 2007;35:7527-44.
26. Brosh RM Jr. DNA helicases involved in DNA repair and their roles in cancer. Nat Rev Cancer 2013;13:542-58.
27. Shamanna RA, Lu H, de Freitas JK, Tian J, Croteau DL, Bohr VA. WRN regulates pathway choice between classical and alternative non-homologous end joining. Nat Commun 2016;7:13785.
28. Palermo V, Rinalducci S, Sanchez M, et al. CDK1 phosphorylates WRN at collapsed replication forks. Nat Commun 2016;7:12880.
29. 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.
30. Sturzenegger A, Burdova K, Kanagaraj R, et al. DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. J Biol Chem 2014;289:27314-26.
31. Lee JH, Shamanna RA, Kulikowicz T, et al. CDK2 phosphorylation of Werner protein (WRN) contributes to WRN’s DNA double-strand break repair pathway choice. Aging Cell 2021;20:e13484.
32. Gupta P, Saha B, Chattopadhyay S, Patro BS. Pharmacological targeting of differential DNA repair, radio-sensitizes WRN-deficient cancer cells in vitro and in vivo. Biochem Pharmacol 2021;186:114450.
33. Chu B, Zhang D, Paukstelis PJ. A DNA G-quadruplex/i-motif hybrid. Nucleic Acids Res 2019;47:11921-30.
34. Kamath-Loeb AS, Shen JC, Schmitt MW, Loeb LA. The Werner syndrome exonuclease facilitates DNA degradation and high fidelity DNA polymerization by human DNA polymerase δ. J Biol Chem 2012;287:12480-90.
35. Shah SN, Opresko PL, Meng X, Lee MY, Eckert KA. DNA structure and the Werner protein modulate human DNA polymerase delta-dependent replication dynamics within the common fragile site FRA16D. Nucleic Acids Res 2010;38:1149-62.
36. Chan NL, Hou C, Zhang T, et al. The Werner syndrome protein promotes CAG/CTG repeat stability by resolving large (CAG)(n)/(CTG)(n) hairpins. J Biol Chem 2012;287:30151-6.
37. Baird DM, Davis T, Rowson J, Jones CJ, Kipling D. Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells. Hum Mol Genet 2004;13:1515-24.
38. Sun L, Nakajima S, Teng Y, et al. WRN is recruited to damaged telomeres via its RQC domain and tankyrase1-mediated poly-ADP-ribosylation of TRF1. Nucleic Acids Res 2017;45:3844-59.
39. Diotti R, Loayza D. Shelterin complex and associated factors at human telomeres. Nucleus 2011;2:119-35.
40. Opresko PL, Mason PA, Podell ER, et al. POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J Biol Chem 2005;280:32069-80.
41. Machwe A, Xiao L, Orren DK. TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 2004;23:149-56.
42. Edwards DN, Orren DK, Machwe A. Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2. Nucleic Acids Res 2014;42:7748-61.
43. Liu B, Yi J, Yang X, et al. MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner. Oncogene 2019;38:2501-15.
44. Li M, Liu B, Yi J, et al. MIB1-mediated degradation of WRN promotes cellular senescence in response to camptothecin treatment. FASEB J 2020;34:11488-97.
45. Patro BS, Frøhlich R, Bohr VA, Stevnsner T. WRN helicase regulates the ATR-CHK1-induced S-phase checkpoint pathway in response to topoisomerase-I-DNA covalent complexes. J Cell Sci 2011;124:3967-79.
46. Cheng WH, Muftic D, Muftuoglu M, et al. WRN is required for ATM activation and the S-phase checkpoint in response to interstrand cross-link-induced DNA double-strand breaks. Mol Biol Cell 2008;19:3923-33.
47. Marabitti V, Lillo G, Malacaria E, et al. ATM pathway activation limits R-loop-associated genomic instability in Werner syndrome cells. Nucleic Acids Res 2019;47:3485-502.
48. Balajee AS, Machwe A, May A, et al. The Werner syndrome protein is involved in RNA polymerase II transcription. Mol Biol Cell 1999;10:2655-68.
49. Shiratori M, Suzuki T, Itoh C, Goto M, Furuichi Y, Matsumoto T. WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex. Oncogene 2002;21:2447-54.
50. Fang EF, Hou Y, Lautrup S, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun 2019;10:5284.
51. Massip L, Garand C, Paquet ER, et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J 2010;24:158-72.
52. Maity J, Das B, Bohr VA, Karmakar P. Acidic domain of WRNp is critical for autophagy and up-regulates age associated proteins. DNA Repair (Amst) 2018;68:1-11.
53. Bellare G, Saha B, Patro BS. Targeting autophagy reverses de novo resistance in homologous recombination repair proficient breast cancers to PARP inhibition. Br J Cancer 2021;124:1260-74.
54. Pai BG, Gupta P, Chakraborty S, Tyagi M, Patro BS. Cross-talk between DNA damage and autophagy and its implication in cancer therapy. In: Bhutia SK, editors. Autophagy in tumor and tumor microenvironment. Singapore: Springer; 2020.
55. Behan FM, Iorio F, Picco G, et al. Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature 2019;568:511-6.
56. Chan EM, Shibue T, McFarland JM, et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature 2019;568:551-6.
57. Kategaya L, Perumal SK, Hager JH, Belmont LD. Werner syndrome helicase is required for the survival of cancer cells with microsatellite instability. iScience 2019;13:488-97.
58. Lieb S, Blaha-Ostermann S, Kamper E, et al. Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells. Elife 2019;8:e43333.
59. McDonald ER 3rd, de Weck A, Schlabach MR, et al. Project DRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell 2017;170:577-92.e10.
60. Cowley GS, Weir BA, Vazquez F, et al. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Sci Data 2014;1:140035.
61. van Wietmarschen N, Sridharan S, Nathan WJ, et al. Repeat expansions confer WRN dependence in microsatellite-unstable cancers. Nature 2020;586:292-8.
62. Picco G, Cattaneo CM, van Vliet EJ, et al. Cell Model Network UK Group. Werner helicase is a synthetic-lethal vulnerability in mismatch repair-deficient colorectal cancer refractory to targeted therapies, chemotherapy, and immunotherapy. Cancer Discov 2021;11:1923-37.
63. Franchitto A, Pirzio LM, Prosperi E, Sapora O, Bignami M, Pichierri P. Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway. J Cell Biol 2008;183:241-52.
64. Aggarwal M, Sommers JA, Shoemaker RH, Brosh RM Jr. 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 U S A 2011;108:1525-30.
65. Moles R, Bai XT, Chaib-Mezrag H, Nicot C. WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells. J Hematol Oncol 2016;9:121.
66. Futami K, Takagi M, Shimamoto A, Sugimoto M, Furuichi Y. Increased chemotherapeutic activity of camptothecin in cancer cells by siRNA-induced silencing of WRN helicase. Biol Pharm Bull 2007;30:1958-61.
67. Bou-Hanna C, Jarry A, Lode L, et al. Acute cytotoxicity of MIRA-1/NSC19630, a mutant p53-reactivating small molecule, against human normal and cancer cells via a caspase-9-dependent apoptosis. Cancer Lett 2015;359:211-7.
68. Aggarwal M, Banerjee T, Sommers JA, Brosh RM Jr. Targeting an Achilles’ heel of cancer with a WRN helicase inhibitor. Cell Cycle 2013;12:3329-35.