Escherichia coli YcaQ is a DNA glycosylase that unhooks DNA interstrand crosslinks.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
27 07 2020
27 07 2020
Historique:
accepted:
23
04
2020
revised:
17
04
2020
received:
25
03
2020
pubmed:
16
5
2020
medline:
24
9
2020
entrez:
16
5
2020
Statut:
ppublish
Résumé
Interstrand DNA crosslinks (ICLs) are a toxic form of DNA damage that block DNA replication and transcription by tethering the opposing strands of DNA. ICL repair requires unhooking of the tethered strands by either nuclease incision of the DNA backbone or glycosylase cleavage of the crosslinked nucleotide. In bacteria, glycosylase-mediated ICL unhooking was described in Streptomyces as a means of self-resistance to the genotoxic natural product azinomycin B. The mechanistic details and general utility of glycosylase-mediated ICL repair in other bacteria are unknown. Here, we identify the uncharacterized Escherichia coli protein YcaQ as an ICL repair glycosylase that protects cells against the toxicity of crosslinking agents. YcaQ unhooks both sides of symmetric and asymmetric ICLs in vitro, and loss or overexpression of ycaQ sensitizes E. coli to the nitrogen mustard mechlorethamine. Comparison of YcaQ and UvrA-mediated ICL resistance mechanisms establishes base excision as an alternate ICL repair pathway in bacteria.
Identifiants
pubmed: 32409837
pii: 5836774
doi: 10.1093/nar/gkaa346
pmc: PMC7367128
doi:
Substances chimiques
Escherichia coli Proteins
0
DNA Glycosylases
EC 3.2.2.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
7005-7017Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM131071
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007028
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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