Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Two independent DNA repair pathways cause mutagenesis in template switching deficient Saccharomyces cerevisiae.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2021- : [Oxford] : Oxford University Press
      Original Publication: Austin, Tex. [etc.]
    • الموضوع:
      Saccharomyces cerevisiae*/metabolism ; Saccharomyces cerevisiae Proteins*/genetics ; Saccharomyces cerevisiae Proteins*/metabolism; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; DNA Helicases/genetics ; DNA Repair ; DNA Replication/genetics ; Mutagenesis ; DNA Damage
    • نبذة مختصرة :
      Upon DNA replication stress, cells utilize the postreplication repair pathway to repair single-stranded DNA and maintain genome integrity. Postreplication repair is divided into 2 branches: error-prone translesion synthesis, signaled by proliferating cell nuclear antigen (PCNA) monoubiquitination, and error-free template switching, signaled by PCNA polyubiquitination. In Saccharomyces cerevisiae, Rad5 is involved in both branches of repair during DNA replication stress. When the PCNA polyubiquitination function of Rad5 s disrupted, Rad5 recruits translesion synthesis polymerases to stalled replication forks, resulting in mutagenic repair. Details of how mutagenic repair is carried out, as well as the relationship between Rad5-mediated mutagenic repair and the canonical PCNA-mediated mutagenic repair, remain to be understood. We find that Rad5-mediated mutagenic repair requires the translesion synthesis polymerase ζ but does not require other yeast translesion polymerase activities. Furthermore, we show that Rad5-mediated mutagenic repair is independent of PCNA binding by Rev1 and so is separable from canonical mutagenic repair. In the absence of error-free template switching, both modes of mutagenic repair contribute additively to replication stress response in a replication timing-independent manner. Cellular contexts where error-free template switching is compromised are not simply laboratory phenomena, as we find that a natural variant in RAD5 is defective in PCNA polyubiquitination and therefore defective in error-free repair, resulting in Rad5- and PCNA-mediated mutagenic repair. Our results highlight the importance of Rad5 in regulating spontaneous mutagenesis and genetic diversity in S. cerevisiae through different modes of postreplication repair.
      Competing Interests: Conflicts of interest The authors declare no conflict of interest.
      (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
    • Grant Information:
      FDN-159913 Canadian Institutes for Health Research
    • Contributed Indexing:
      Keywords: DNA repair; Rad5; Rev1; mutagenesis; polymerase zeta; postreplication repair; replication stress; translesion synthesis
    • الرقم المعرف:
      0 (Proliferating Cell Nuclear Antigen)
      EC 3.6.4.- (DNA Helicases)
      0 (Saccharomyces cerevisiae Proteins)
      EC 3.6.1.- (RAD5 protein, S cerevisiae)
    • الموضوع:
      Date Created: 20230818 Date Completed: 20231106 Latest Revision: 20231113
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.1093/genetics/iyad153
    • الرقم المعرف:
      37594077