Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator Journal Article

   


Authors: Wan, B.; Guan, D.; Li, S.; Chwat-Edelstein, T.; Zhao, X.
Article Title: Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator
Abstract: The DNA damage checkpoint is a highly conserved signaling pathway induced by genotoxin exposure or endogenous genome stress. It alters many cellular processes such as arresting the cell cycle progression and increasing DNA repair capacities. However, cells can downregulate the checkpoint after prolonged stress exposure to allow continued growth and alternative repair. Strategies that can dampen the DNA damage checkpoint are not well understood. Here, we report that budding yeast employs a pathway composed of the scaffold protein Rtt107, its binding partner Mms22, and an Mms22-associated ubiquitin ligase complex to downregulate the DNA damage checkpoint. Mechanistically, this pathway promotes the proteasomal degradation of a key checkpoint factor, Rad9. Furthermore, Rtt107 binding to Mms22 helps to enrich the ubiquitin ligase complex on chromatin for targeting the chromatin-bound form of Rad9. Finally, we provide evidence that the Rtt107-Mms22 axis operates in parallel with the Rtt107-Slx4 axis, which displaces Rad9 from chromatin. We thus propose that Rtt107 enables a bifurcated “anti-Rad9” strategy to optimally downregulate the DNA damage checkpoint. © The Author(s) 2024.
Keywords: signal transduction; controlled study; protein phosphorylation; unclassified drug; dna binding protein; genetics; dna-binding proteins; nonhuman; dna replication; cell cycle protein; phenotype; metabolism; cell cycle proteins; allele; dna damage; cell survival; cell cycle progression; cell cycle s phase; complex formation; dna repair; proteasome; signaling; nuclear protein; ubiquitin protein ligase; protein degradation; protein depletion; protein protein interaction; protein targeting; cell protein; protein; protein stability; nuclear proteins; dna; protein synthesis; saccharomyces cerevisiae; chromatin; genomic instability; cell cycle checkpoint; nuclease; chromosome rearrangement; binding protein; binding site; genome; checkpoint kinase 2; cell cycle g2 phase; cell cycle m phase; down regulation; yeast; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; ubiquitin protein ligase e3; ubiquitin-protein ligases; cell cycle g1 phase; dpb11 protein; cell mutant; protein rad9; growth rate; deoxyribonuclease; endodeoxyribonucleases; budding yeast; dna damage checkpoint; scaffold protein; cell cycle checkpoints; cell component; article; asf1 protein; rtt107 protein; slx4 protein; ddc1 protein; k1088m protein; mms1 protein; mms22 protein; rtt101 protein; t602a protein; mms22 protein, s cerevisiae; rtt107 protein, s cerevisiae; slx4 protein, s cerevisiae
Journal Title: Nature Communications
Volume: 16
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2025-01-02
Start Page: 311
Language: English
DOI: 10.1038/s41467-024-54624-0
PUBMED: 39746913
PROVIDER: scopus
PMCID: PMC11697250
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85214034914&doi=10.1038%2fs41467-024-54624-0&partnerID=40&md5=1dc6feff1f5abb7af2e1708aee5bb999
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Xiaolan Zhao -- Source: Scopus
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MSK Authors
  1. Xiaolan Zhao
    77 Zhao
  2. Bingbing Wan
    6 Wan
  3. Shibai Li
    10 Li
  4. Danying Guan
    3 Guan
  5. Tzippora Chwat-Edelstein
    1 Chwat-Edelstein
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