Rtt105 regulates RPA function by configurationally stapling the flexible domains


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.



Rtt105, RPA function, flexible domains, Replication Protein A


Kuppa, Sahiti, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R. Mattice, Nilisha Pokhrel, Vikas Kaushik, Angela Patterson et al. "Rtt105 regulates RPA function by configurationally stapling the flexible domains." Nature communications 13, no. 1 (2022): 1-16.
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