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Cited by 4DNA Repair MechanismsUbiquitin and proteasome pathwaysTelomeres, Telomerase, and Senescence

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USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication

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Mackay, Hannah L., Stone, Helen R., Ronson, George E., Ellis, Katherine, Lanz, Alexander, Aghabi, Yara, Walker, Alexandra K., Starowicz, Katarzyna, Garvin, Alexander J., Van Eijk, Patrick, Koestler, Stefan A., Anthony, Elizabeth J., Piberger, Ann Liza, Chauhan, Anoop S., Conway-Thomas, Poppy, Vaitsiankova, Alina, Vijayendran, Sobana, Beesley, James F., Petermann, Eva, Brown, Eric J., Densham, Ruth M., Reed, Simon H., Dobbs, Felix, Saponaro, Marco, Morris, Joanna R.·2024·Nature Communications
DOI 10.1038/s41467-024-52250-4PMC PMC11405836

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Abstract

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

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Research works printed but not linked: 127

  1. Zeman, M. K. & Cimprich, K. A. Causes and consequences of replication stress. Nat. Cell Biol. 16, 2–9 (2014). · DOI · Paper page
  2. Gaillard, H., Garcia-Muse, T. & Aguilera, A. Replication stress and cancer. Nat. Rev. Cancer 15, 276–289 (2015). · DOI
  3. Lu, H. & Davis, A. J. Human RecQ helicases in DNA double-strand break repair. Front. Cell Dev. Biol. 9, 640755 (2021). · DOI
  4. Larsen, N. B. & Hickson, I. D. RecQ helicases: conserved guardians of genomic integrity. Adv. Exp. Med. Biol. 767, 161–184 (2013). · DOI
  5. Vindigni, A. & Hickson, I. D. RecQ helicases: multiple structures for multiple functions? HFSP J. 3, 153–164 (2009). · DOI
  6. Mojumdar, A. Mutations in conserved functional domains of human RecQ helicases are associated with diseases and cancer: a review. Biophys. Chem. 265, 106433 (2020). · DOI
  7. Capp, C., Wu, J. & Hsieh, T. S. RecQ4: the second replicative helicase? Crit. Rev. Biochem. Mol. Biol. 45, 233–242 (2010). · DOI
  8. Abu-Libdeh B. et al. RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1. J. Clin. Invest. 132, e147301 (2022). · DOI
  9. Lieb S. et al. Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells. Elife 8, e43333 (2019). · DOI
  10. Kategaya, L., Perumal, S. K., Hager, J. H. & Belmont, L. D. Werner syndrome helicase is required for the survival of cancer cells with microsatellite instability. iScience 13, 488–497 (2019). · DOI
  11. van Wietmarschen, N. et al. Repeat expansions confer WRN dependence in microsatellite-unstable cancers. Nature 586, 292–298 (2020). · DOI
  12. Davies, S. L., North, P. S. & Hickson, I. D. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat. Struct. Mol. Biol. 14, 677–679 (2007). · DOI
  13. Berti, M. et al. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat. Struct. Mol. Biol. 20, 347–354 (2013). · DOI
  14. Zellweger, R. et al. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. J. Cell Biol. 208, 563–579 (2015). · DOI
  15. Rodriguez-Lopez, A. M., Jackson, D. A., Iborra, F. & Cox, L. S. Asymmetry of DNA replication fork progression in Werner’s syndrome. Aging Cell 1, 30–39 (2002). · DOI
  16. Sidorova, J. M., Li, N., Folch, A. & Monnat, R. J. Jr. The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest. Cell Cycle 7, 796–807 (2008). · DOI
  17. Su, F. et al. Nonenzymatic role for WRN in preserving nascent DNA strands after replication stress. Cell Rep. 9, 1387–1401 (2014). · DOI
  18. Baynton, K. et al. WRN interacts physically and functionally with the recombination mediator protein RAD52. J. Biol. Chem. 278, 36476–36486 (2003). · DOI
  19. Pichierri, P., Nicolai, S., Cignolo, L., Bignami, M. & Franchitto, A. The RAD9-RAD1-HUS1 (9.1.1) complex interacts with WRN and is crucial to regulate its response to replication fork stalling. Oncogene 31, 2809–2823 (2012). · DOI
  20. Thangavel, S. et al. DNA2 drives processing and restart of reversed replication forks in human cells. J. Cell Biol. 208, 545–562 (2015). · DOI
  21. Blundred, R., Myers, K., Helleday, T., Goldman, A. S. & Bryant, H. E. Human RECQL5 overcomes thymidine-induced replication stress. DNA Repair (Amst.) 9, 964–975 (2010). · DOI
  22. Popuri, V. et al. RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic Acids Res. 41, 881–899 (2013). · DOI
  23. Kanagaraj, R., Saydam, N., Garcia, P. L., Zheng, L. & Janscak, P. Human RECQ5beta helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication fork. Nucleic Acids Res. 34, 5217–5231 (2006). · DOI
  24. Ozsoy, A. Z., Ragonese, H. M. & Matson, S. W. Analysis of helicase activity and substrate specificity of Drosophila RECQ5. Nucleic Acids Res. 31, 1554–1564 (2003). · DOI
  25. Rossi, M. L., Ghosh, A. K. & Bohr, V. A. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair (Amst.) 9, 331–344 (2010). · DOI
  26. Rogers, C. M. et al. Yeast Hrq1 shares structural and functional homology with the disease-linked human RecQ4 helicase. Nucleic Acids Res. 45, 5217–5230 (2017). · DOI
  27. Nickoloff J. A. et al. Cellular responses to widespread DNA replication stress. Int. J. Mol. Sci. 24, 16903 (2023). · DOI
  28. Zheng, L. et al. Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. EMBO Rep. 6, 83–89 (2005). · DOI
  29. Bryant, H. E. et al. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J. 28, 2601–2615 (2009). · DOI
  30. Duxin, J. P. et al. Okazaki fragment processing-independent role for human Dna2 enzyme during DNA replication. J. Biol. Chem. 287, 21980–21991 (2012). · DOI
  31. Peng, G. et al. Human nuclease/helicase DNA2 alleviates replication stress by promoting DNA end resection. Cancer Res. 72, 2802–2813 (2012). · DOI
  32. Duxin, J. P. et al. Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. Mol. Cell Biol. 29, 4274–4282 (2009). · DOI
  33. Li Z. et al. hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability. EMBO J. 37, e96729 (2018). · DOI
  34. Shaheen, R. et al. Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res. 24, 291–299 (2014). · DOI
  35. Tarnauskaite, Z. et al. Biallelic variants in DNA2 cause microcephalic primordial dwarfism. Hum. Mutat. 40, 1063–1070 (2019).
  36. Di Lazzaro Filho R. et al. Biallelic variants in DNA2 cause poikiloderma with congenital cataracts and severe growth failure reminiscent of Rothmund-Thomson syndrome. J. Med. Genet. 60, 1127–1132 (2023). · DOI
  37. Ulrich, H. D. Two-way communications between ubiquitin-like modifiers and DNA. Nat. Struct. Mol. Biol. 21, 317–324 (2014). · DOI
  38. Smeenk, G. & Mailand, N. Writers, readers, and erasers of histone ubiquitylation in DNA double-strand break repair. Front. Genet. 7, 122 (2016). · DOI
  39. Yuan, J. et al. HERC2-USP20 axis regulates DNA damage checkpoint through claspin. Nucleic Acids Res. 42, 13110–13121 (2014). · DOI
  40. Quesada, V. C. et al. Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases. Biochem. Biophys. Res. Commun. 314, 54–62 (2004). · DOI
  41. Ernst, A. et al. A strategy for modulation of enzymes in the ubiquitin system. Science 339, 590–595 (2013). · DOI
  42. Komander, D., Clague, M. J. & Urbe, S. Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 10, 550–563 (2009). · DOI · Paper page
  43. Kilgas, S. & Ramadan, K. Inhibitors of the ATPase p97/VCP: From basic research to clinical applications. Cell Chem. Biol. 30, 3–21 (2023). · DOI
  44. Petermann, E. et al. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol. Cell 37, 492–502 (2010). · DOI
  45. Xu, Q., Farah, M., Webster, J. M. & Wojcikiewicz, R. J. Bortezomib rapidly suppresses ubiquitin thiolesterification to ubiquitin-conjugating enzymes and inhibits ubiquitination of histones and type I inositol 1,4,5-trisphosphate receptor. Mol. Cancer Ther. 3, 1263–1269 (2004). · DOI
  46. Karlsson M. et al. A single-cell type transcriptomics map of human tissues. Sci. Adv. 7, eabh2169 (2021). · DOI · Paper page
  47. Byun, T. S., Pacek, M., Yee, M. C., Walter, J. C. & Cimprich, K. A. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 19, 1040–1052 (2005). · DOI · Paper page
  48. Altieri, A., Dell’Aquila, M., Pentimalli, F., Giordano, A. & Alfano, L. SMART (Single Molecule Analysis of Resection Tracks) technique for assessing DNA end-resection in response to DNA damage. Bio Protoc. 10, e3701 (2020). · DOI
  49. Nickoloff, J. A., Sharma, N., Taylor, L., Allen, S. J. & Hromas, R. The safe path at the fork: ensuring replication-associated DNA double-strand breaks are repaired by homologous recombination. Front. Genet. 12, 748033 (2021). · DOI
  50. Hanada, K. et al. The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Nat. Struct. Mol. Biol. 14, 1096–1104 (2007). · DOI
  51. Franchitto, A. et al. Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway. J. Cell Biol. 183, 241–252 (2008). · DOI
  52. Rass, U. Resolving branched DNA intermediates with structure-specific nucleases during replication in eukaryotes. Chromosoma 122, 499–515 (2013). · DOI
  53. Cai, J. et al. Induction of deubiquitinating enzyme USP50 during erythropoiesis and its potential role in the regulation of Ku70 stability. J. Investig. Med. 66, 1–6 (2018). · DOI
  54. Lee, J. Y. et al. The deubiquitinating enzyme, ubiquitin-specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein. FEBS Lett. 591, 479–490 (2017). · DOI
  55. Keijzer N. et al. Variety in the USP deubiquitinase catalytic mechanism. Life Sci. Alliance 7, (2024). · DOI
  56. Dobbs, F. M. et al. Precision digital mapping of endogenous and induced genomic DNA breaks by INDUCE-seq. Nat. Commun. 13, 3989 (2022). · DOI
  57. Li B., Reddy S. & Comai L. The Werner syndrome helicase coordinates sequential strand displacement and FEN1-mediated flap cleavage during polymerase delta elongation. Mol Cell Biol 37, e00560-16 (2017). · DOI
  58. Sarkies, P. et al. FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA. Nucleic Acids Res. 40, 1485–1498 (2012). · DOI
  59. Wang, W. et al. The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Proc. Natl Acad. Sci. USA 101, 16762–16767 (2004). · DOI · Paper page
  60. 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. 43, 9788–9803 (2015).
  61. Sharma, S. et al. WRN helicase and FEN-1 form a complex upon replication arrest and together process branch migrating DNA structures associated with the replication fork. Mol. Biol. Cell 15, 734–750 (2004). · DOI
  62. Brosh R. M. Jr. et al. Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity. EMBO J. 20, 5791–5801 (2001). · DOI
  63. Saharia, A. et al. FEN1 ensures telomere stability by facilitating replication fork re-initiation. J. Biol. Chem. 285, 27057–27066 (2010). · DOI
  64. Xu, S. et al. Abro1 maintains genome stability and limits replication stress by protecting replication fork stability. Genes Dev. 31, 1469–1482 (2017). · DOI
  65. Garzon, J., Ursich, S., Lopes, M., Hiraga, S. I. & Donaldson, A. D. Human RIF1-protein phosphatase 1 prevents degradation and breakage of nascent DNA on replication stalling. Cell Rep. 27, 2558–2566.e2554 (2019). · DOI
  66. Mukherjee, C. et al. RIF1 promotes replication fork protection and efficient restart to maintain genome stability. Nat. Commun. 10, 3287 (2019). · DOI
  67. Dungrawala, H. & Cortez, D. Purification of proteins on newly synthesized DNA using iPOND. Methods Mol. Biol. 1228, 123–131 (2015). · DOI
  68. Sirbu, B. M. et al. Identification of proteins at active, stalled, and collapsed replication forks using isolation of proteins on nascent DNA (iPOND) coupled with mass spectrometry. J. Biol. Chem. 288, 31458–31467 (2013). · DOI
  69. Dungrawala, H. et al. The replication checkpoint prevents two types of fork collapse without regulating replisome stability. Mol. Cell 59, 998–1010 (2015). · DOI
  70. Kehrli, K. et al. Class I histone deacetylase HDAC1 and WRN RECQ helicase contribute additively to protect replication forks upon hydroxyurea-induced arrest. J. Biol. Chem. 291, 24487–24503 (2016). · DOI
  71. Wang, Q. et al. Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance. Aging (Albany NY) 15, 10767–10784 (2023). · DOI
  72. Wiest, N. E. & Tomkinson, A. E. Optimization of native and formaldehyde iPOND techniques for use in suspension cells. Methods Enzymol. 591, 1–32 (2017). · DOI
  73. Chung, L. et al. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Oncogene 34, 902–911 (2015). · DOI
  74. Hanzlikova, H. et al. The importance of poly(ADP-ribose) polymerase as a sensor of unligated okazaki fragments during DNA replication. Mol. Cell 71, 319–331.e313 (2018). · DOI
  75. Crabbe, L., Verdun, R. E., Haggblom, C. I. & Karlseder, J. Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306, 1951–1953 (2004). · DOI
  76. Saharia, A. et al. Flap endonuclease 1 contributes to telomere stability. Curr. Biol. 18, 496–500 (2008). · DOI
  77. Damerla, R. R. et al. Werner syndrome protein suppresses the formation of large deletions during the replication of human telomeric sequences. Cell Cycle 11, 3036–3044 (2012). · DOI
  78. Sturzenegger, A. et al. DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. J. Biol. Chem. 289, 27314–27326 (2014). · DOI
  79. Pinto C., Kasaciunaite K., Seidel R. & Cejka P. Human DNA2 possesses a cryptic DNA unwinding activity that functionally integrates with BLM or WRN helicases. Elife 5, e18574 (2016). · DOI
  80. Liu, W. et al. A selective small molecule DNA2 inhibitor for sensitization of human cancer cells to chemotherapy. EBioMedicine 6, 73–86 (2016). · DOI
  81. Masuda-Sasa, T., Polaczek, P., Peng, X. P., Chen, L. & Campbell, J. L. Processing of G4 DNA by Dna2 helicase/nuclease and replication protein A (RPA) provides insights into the mechanism of Dna2/RPA substrate recognition. J. Biol. Chem. 283, 24359–24373 (2008). · DOI
  82. Lin, W. et al. Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J. 32, 1425–1439 (2013). · DOI
  83. Nimonkar, A. V. et al. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 25, 350–362 (2011). · DOI
  84. Sidorova J. M., Kehrli K., Mao F. & Monnat R., Jr. Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling. DNA Repair 12, 128–139 (2013). · DOI
  85. Hu, Y. et al. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev. 21, 3073–3084 (2007). · DOI
  86. Saponaro, M. et al. RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 157, 1037–1049 (2014). · DOI · Paper page
  87. Urban, V. et al. RECQ5 helicase promotes resolution of conflicts between replication and transcription in human cells. J. Cell Biol. 214, 401–415 (2016). · DOI
  88. Ghosh, A. K. et al. RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance. J. Biol. Chem. 287, 196–209 (2012). · DOI
  89. Masai, H. RecQL4: a helicase linking formation and maintenance of a replication fork. J. Biochem. 149, 629–631 (2011). · DOI
  90. Popuri, V. et al. RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic Acids Res. 45, 1566 (2017). · DOI
  91. Singh, D. K. et al. The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability. Nucleic Acids Res. 40, 6632–6648 (2012). · DOI
  92. Zyner K. G. et al. Genetic interactions of G-quadruplexes in humans. Elife 8, e46793 (2019). · DOI
  93. Groza, T. et al. The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease. Nucleic Acids Res. 51, D1038–D1045 (2023). · DOI · Paper page
  94. Aressy, B. et al. A screen for deubiquitinating enzymes involved in the G(2)/M checkpoint identifies USP50 as a regulator of HSP90-dependent Wee1 stability. Cell Cycle 9, 3815–3822 (2010). · DOI
  95. Buus, R., Faronato, M., Hammond, D. E., Urbe, S. & Clague, M. J. Deubiquitinase activities required for hepatocyte growth factor-induced scattering of epithelial cells. Curr. Biol. 19, 1463–1466 (2009). · DOI
  96. Walden, M., Masandi, S. K., Pawlowski, K. & Zeqiraj, E. Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes. Biochem. Soc. Trans. 46, 453–466 (2018). · DOI
  97. Singh, P., Zheng, L., Chavez, V., Qiu, J. & Shen, B. Concerted action of exonuclease and Gap-dependent endonuclease activities of FEN-1 contributes to the resolution of triplet repeat sequences (CTG)n- and (GAA)n-derived secondary structures formed during maturation of Okazaki fragments. J. Biol. Chem. 282, 3465–3477 (2007). · DOI
  98. Liu, R., Qiu, J., Finger, L. D., Zheng, L. & Shen, B. The DNA-protein interaction modes of FEN-1 with gap substrates and their implication in preventing duplication mutations. Nucleic Acids Res. 34, 1772–1784 (2006). · DOI
  99. Huang, S. et al. Characterization of the human and mouse WRN 3’–>5’ exonuclease. Nucleic Acids Res. 28, 2396–2405 (2000). · DOI
  100. Shen, J. C. & Loeb, L. A. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases. Trends Genet. 16, 213–220 (2000). · DOI
  101. Yoon, J. H., Sellamuthu, K., Prakash, L. & Prakash, S. WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases. Genes Dev. 38, 213–232 (2024). · DOI
  102. Kamath-Loeb, A. S., Lan, L., Nakajima, S., Yasui, A. & Loeb, L. A. Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc. Natl Acad. Sci. USA 104, 10394–10399 (2007). · DOI
  103. Gray, M. D. et al. The Werner syndrome protein is a DNA helicase. Nat. Genet. 17, 100–103 (1997). · DOI
  104. Brosh, R. M. Jr., Opresko, P. L. & Bohr, V. A. Enzymatic mechanism of the WRN helicase/nuclease. Methods Enzymol. 409, 52–85 (2006). · DOI
  105. Datta, A. et al. WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells. Nat. Commun. 12, 6561 (2021). · DOI
  106. Hansel-Hertsch, R., Spiegel, J., Marsico, G., Tannahill, D. & Balasubramanian, S. Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing. Nat. Protoc. 13, 551–564 (2018). · DOI
  107. Lyu, J., Shao, R., Yung, Kwong & Elsasser, P. Y. SJ. Genome-wide mapping of G-quadruplex structures with CUT&Tag. Nucleic Acids Res. 50, e13 (2022). · DOI
  108. Marsico, G. et al. Whole genome experimental maps of DNA G-quadruplexes in multiple species. Nucleic Acids Res. 47, 3862–3874 (2019). · DOI
  109. Falquet, B. et al. Disease-associated DNA2 nuclease-helicase protects cells from lethal chromosome under-replication. Nucleic Acids Res. 48, 7265–7278 (2020).
  110. Thakar, T. et al. Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly. Nat. Commun. 11, 2147 (2020). · DOI
  111. Sangrithi, M. N. et al. Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell 121, 887–898 (2005). · DOI
  112. Xu, X. & Liu, Y. Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4. EMBO J. 28, 568–577 (2009). · DOI
  113. Thangavel, S. et al. Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol. Cell Biol. 30, 1382–1396 (2010). · DOI
  114. Luong, T. T. et al. Hrq1/RECQL4 regulation is critical for preventing aberrant recombination during DNA intrastrand crosslink repair and is upregulated in breast cancer. PLoS Genet. 18, e1010122 (2022). · DOI
  115. Lu, H. et al. RECQL4 promotes DNA end resection in repair of DNA double-strand breaks. Cell Rep. 16, 161–173 (2016). · DOI
  116. Speina, E. et al. Human RECQL5beta stimulates flap endonuclease 1. Nucleic Acids Res. 38, 2904–2916 (2010). · DOI
  117. Rossi, M. L., Ghosh, A. K., Kulikowicz, T., Croteau, D. L. & Bohr, V. A. Conserved helicase domain of human RecQ4 is required for strand annealing-independent DNA unwinding. DNA Repair (Amst.) 9, 796–804 (2010). · DOI
  118. Budhathoki, J. B. et al. RecQ-core of BLM unfolds telomeric G-quadruplex in the absence of ATP. Nucleic Acids Res. 42, 11528–11545 (2014). · DOI
  119. Sowa, M. E., Bennett, E. J., Gygi, S. P. & Harper, J. W. Defining the human deubiquitinating enzyme interaction landscape. Cell 138, 389–403 (2009). · DOI
  120. Butler, L. R. et al. The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response. EMBO J. 31, 3918–3934 (2012). · DOI
  121. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012). · DOI · Paper page
  122. Rueden, C. T. et al. ImageJ2: ImageJ for the next generation of scientific image data. BMC bioinformatics 18, 529 (2017). · DOI
  123. Cruz-García, A., López-Saavedra, A. & Huertas, P. BRCA1 accelerates CtIP-mediated DNA-end resection. Cell Rep. 9, 451–459 (2014). · DOI
  124. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012). · DOI · Paper page
  125. Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010). · DOI · Paper page
  126. Santana-Garcia, W. et al. RSAT 2022: regulatory sequence analysis tools. Nucleic Acids Res. 50, W670–W676 (2022). · DOI
  127. Williams E. S., Bailey S. M. Chromosome orientation fluorescence in situ hybridization (CO-FISH). Cold Spring Harb. Protoc. 2009, pdb prot5269 (2009). · DOI

Metadata

Authors
Mackay, H. L., Stone, H. R., Ronson, G. E., Ellis, K., Lanz, A., Aghabi, Y., Walker, A. K., Starowicz, K., Garvin, A. J., Van Eijk, P., Koestler, S. A., Anthony, E. J., Piberger, A. L., Chauhan, A. S., Conway-Thomas, P., Vaitsiankova, A., Vijayendran, S., Beesley, J. F., Petermann, E., Brown, E. J., Densham, R. M., Reed, S. H., Dobbs, F., Saponaro, M., & Morris, J. R.
Affiliations
  • University of Birmingham (GB)
  • Cancer Research UK Clinical Trials Unit (GB)
  • University of Leeds (GB)
  • Cardiff University (GB)
  • University of Sussex (GB)
  • Queen Elizabeth Hospital Birmingham (GB)
  • University of Pennsylvania (US)
Corresponding author
Morris, Joanna R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-09-16
Volume
15
Issue
1
Pages
8102-8102
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-52250-4
PMC
PMC11405836
OpenAlex
W4402581122
Cited by
4
References
4
Citations by year
2026: 2 · 2025: 2
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion, cc-by)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion, cc-by)
  • PubMed Central (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Cancer Research UK
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords
ubiquitin-specific protease, RecQ helicase, RECQL4, RECQL5, DNA2 nuclease, FEN1, WRN, DNA replication, replication fork restart, stalled replication forks, telomere maintenance, replicative stress, hydroxyurea, pyridostatin, chromatin proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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