The Rad51 paralogs facilitate a novel DNA strand specific damage tolerance pathway

Joel C. Rosenbaum, Braulio Bonilla, Sarah R. Hengel, Tony M. Mertz, Benjamin W. Herken, Hinke G. Kazemier, Catherine A. Pressimone, Timothy C. Ratterman, Ellen MacNary, Alessio De Magis, Youngho Kwon, Stephen K. Godin, Bennett Van Houten, Daniel P. Normolle, Patrick Sung, Subha R. Das, Katrin Paeschke, Steven A. Roberts, Andrew P. VanDemark, Kara A. Bernstein*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    Accurate DNA replication is essential for genomic stability and cancer prevention. Homologous recombination is important for high-fidelity DNA damage tolerance during replication. How the homologous recombination machinery is recruited to replication intermediates is unknown. Here, we provide evidence that a Rad51 paralog-containing complex, the budding yeast Shu complex, directly recognizes and enables tolerance of predominantly lagging strand abasic sites. We show that the Shu complex becomes chromatin associated when cells accumulate abasic sites during S phase. We also demonstrate that purified recombinant Shu complex recognizes an abasic analog on a double-flap substrate, which prevents AP endo-nuclease activity and endonuclease-induced double-strand break formation. Shu complex DNA binding mutants are sensitive to methyl methanesulfonate, are not chromatin enriched, and exhibit increased mutation rates. We propose a role for the Shu complex in recognizing abasic sites at replication intermediates, where it recruits the homologous recombination machinery to mediate strand specific damage tolerance.

    Original languageEnglish
    Article number3515
    Number of pages11
    JournalNature Communications
    Volume10
    DOIs
    Publication statusPublished - 5-Aug-2019

    Keywords

    • BASE EXCISION-REPAIR
    • ABASIC ENDONUCLEASE ACTIVITY
    • HOMOLOGOUS RECOMBINATION
    • SACCHAROMYCES-CEREVISIAE
    • PROTEINS
    • SITES
    • MUTATION
    • ROLES
    • YEAST
    • REPLICATION

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