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Nat Commun. 2019 Aug 5.

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

Rosenbaum JC, Bonilla B, Hengel SR, Mertz TM, Herken BW, Kazemier HG, Pressimone CA, Ratterman TC, MacNary E, De Magis A, Kwon Y, Godin SK, Van Houten B, Normolle DP, Sung P, Das SR, Paeschke K, Roberts SA, VanDemark AP, Bernstein KA

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 endonuclease 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.

PMID: 31383866