期刊论文详细信息
eLife
The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
Hani S Zaher1  Piotr A Mieczkowski2  Ewa P Malc2  Rudri K Vyas3  Tony M Mertz3  Steven A Roberts3  Debra Mitchell3  Alexander J Brown3  Kara A Bernstein4  Braulio Bonilla4  Sarah R Hengel4  Thong T Luong4  Adeola A Fagunloye4  Catherine A Pressimone4  Kyle S Rapchak4  Reagan A Russell5  Nima Mosammaparast6 
[1] Biology, Washington University in St Louis, St. Louis, United States;Genetics, University of North Carolina Chapel Hill, Chapel Hill, United States;Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, United States;Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States;University of Pittsburgh School of Medicine, Pittsburgh, United States;Washington University in St Louis, St Louis, United States;
关键词: Rad51 paralogs;    Shu complex;    DNA repair;    alkyation damage;    homologous recombination;    Rad51;    S. cerevisiae;   
DOI  :  10.7554/eLife.68080
来源: eLife Sciences Publications, Ltd
PDF
【 摘 要 】

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.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202112117557869ZK.pdf 1824KB PDF download
  文献评价指标  
  下载次数:12次 浏览次数:1次