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Publication Detail

Title: The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions.

Authors: Bonilla, Braulio; Brown, Alexander J; Hengel, Sarah R; Rapchak, Kyle S; Mitchell, Debra; Pressimone, Catherine A; Fagunloye, Adeola A; Luong, Thong T; Russell, Reagan A; Vyas, Rudri K; Mertz, Tony M; Zaher, Hani S; Mosammaparast, Nima; Malc, Ewa P; Mieczkowski, Piotr A; Roberts, Steven A; Bernstein, Kara A

Published In Elife, (2021 11 01)

Abstract: Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to how yeast repairs 3meC, particularly in single-stranded DNA. The yeast Shu complex, a conserved homologous recombination factor, aids in preventing replication-associated mutagenesis from DNA base damaging agents such as methyl methanesulfonate (MMS). We found that MMS-treated Shu complex-deficient cells exhibit a genome-wide increase in A:T and G:C substitutions mutations. The G:C substitutions displayed transcriptional and replicational asymmetries consistent with mutations resulting from 3meC. Ectopic expression of a human AlkB homolog in Shu-deficient yeast rescues MMS-induced growth defects and increased mutagenesis. Thus, our work identifies a novel homologous recombination-based mechanism mediated by the Shu complex for coping with alkylation adducts.

PubMed ID: 34723799 Exiting the NIEHS site

MeSH Terms: Alkylation; Homologous Recombination/drug effects*; Methyl Methanesulfonate/pharmacology*; Mutagenesis; Mutagens/pharmacology*; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/drug effects; Saccharomyces cerevisiae/genetics*; Saccharomyces cerevisiae/metabolism

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