Rtt105 regulates RPA function by configurationally stapling the flexible domains Journal Article

   


Authors: Kuppa, S.; Deveryshetty, J.; Chadda, R.; Mattice, J. R.; Pokhrel, N.; Kaushik, V.; Patterson, A.; Dhingra, N.; Pangeni, S.; Sadauskas, M. K.; Shiekh, S.; Balci, H.; Ha, T.; Zhao, X.; Bothner, B.; Antony, E.
Article Title: Rtt105 regulates RPA function by configurationally stapling the flexible domains
Abstract: Replication Protein A (RPA) is a heterotrimeric complex that binds to single-stranded DNA (ssDNA) and recruits over three dozen RPA-interacting proteins to coordinate multiple aspects of DNA metabolism including DNA replication, repair, and recombination. Rtt105 is a molecular chaperone that regulates nuclear localization of RPA. Here, we show that Rtt105 binds to multiple DNA binding and protein-interaction domains of RPA and configurationally staples the complex. In the absence of ssDNA, Rtt105 inhibits RPA binding to Rad52, thus preventing spurious binding to RPA-interacting proteins. When ssDNA is available, Rtt105 promotes formation of high-density RPA nucleoprotein filaments and dissociates during this process. Free Rtt105 further stabilizes the RPA-ssDNA filaments by inhibiting the facilitated exchange activity of RPA. Collectively, our data suggest that Rtt105 sequesters free RPA in the nucleus to prevent untimely binding to RPA-interacting proteins, while stabilizing RPA-ssDNA filaments at DNA lesion sites. © 2022, The Author(s).
Keywords: genetics; dna replication; metabolism; protein binding; dna; genetic recombination; saccharomyces cerevisiae; recombination, genetic; molecular analysis; replication factor a; single stranded dna; dna, single-stranded; replication protein a; lesion; coordinate
Journal Title: Nature Communications
Volume: 13
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2022-09-02
Start Page: 5152
Language: English
DOI: 10.1038/s41467-022-32860-6
PUBMED: 36056028
PROVIDER: scopus
PMCID: PMC9440123
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85137167778&doi=10.1038%2fs41467-022-32860-6&partnerID=40&md5=6161aa9f73f0c7b8a37fae4c796318f3
Notes: Article -- Export Date: 3 October 2022 -- Source: Scopus
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MSK Authors
  1. Xiaolan Zhao
    77 Zhao
  2. Nalini Dhingra
    10 Dhingra
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