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

Nature Communications
Joel C RosenbaumKara A Bernstein

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 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.

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Citations

Jul 15, 2020·Annual Review of Genetics·Braulio BonillaKara A Bernstein
May 18, 2020·DNA Repair·Petria S Thompson, David Cortez
Dec 3, 2020·International Journal of Molecular Sciences·Jeong-Yeon MunSun-Hee Leem
Feb 1, 2020·Pharmacology & Therapeutics·Erik LauriniSabrina Pricl
Jul 27, 2021·Current Opinion in Genetics & Development·Hayley L ReinRobert A Baldock

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Methods Mentioned

BETA
deamination
deaminations
electrophoretic mobility shift assay
pull-down
PCR
two-hybrid
size exclusion chromatography
electrophoresis

Software Mentioned

Geneious
PRISM7
ImageQuant TL
Photoshop
ImageJ

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