The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions.
DNA repair
Rad51
Rad51 paralogs
S. cerevisiae
Shu complex
alkyation damage
biochemistry
cell biology
chemical biology
homologous recombination
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
04
03
2021
accepted:
29
10
2021
pubmed:
2
11
2021
medline:
27
1
2022
entrez:
1
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34723799
doi: 10.7554/eLife.68080
pii: 68080
pmc: PMC8610418
doi:
pii:
Substances chimiques
Mutagens
0
Saccharomyces cerevisiae Proteins
0
Methyl Methanesulfonate
AT5C31J09G
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIEHS NIH HHS
ID : K99 ES033738
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008336
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193318
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112641
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218112
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030335
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227001
Pays : United States
Informations de copyright
© 2021, Bonilla et al.
Déclaration de conflit d'intérêts
BB, AB, SH, KR, DM, CP, AF, TL, RR, RV, TM, HZ, NM, EM, PM, SR, KB No competing interests declared
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