HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA.
5-Methylcytosine
/ analogs & derivatives
Apurinic Acid
/ metabolism
DNA
/ metabolism
DNA Damage
/ physiology
DNA Repair
/ physiology
DNA Replication
/ physiology
DNA, Single-Stranded
/ metabolism
DNA-Binding Proteins
/ genetics
Endonucleases
Escherichia coli
/ metabolism
Polynucleotides
/ metabolism
Proliferating Cell Nuclear Antigen
/ metabolism
5-hydroxymethylcytosine
DNA repair
DNA replication
DNA-protein crosslink
HMCES
PCNA
REV1
SRAP
replication stress
translesion DNA synthesis
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
07
08
2018
revised:
15
10
2018
accepted:
29
10
2018
pubmed:
18
12
2018
medline:
14
11
2019
entrez:
18
12
2018
Statut:
ppublish
Résumé
Abasic sites are one of the most common DNA lesions. All known abasic site repair mechanisms operate only when the damage is in double-stranded DNA. Here, we report the discovery of 5-hydroxymethylcytosine (5hmC) binding, ESC-specific (HMCES) as a sensor of abasic sites in single-stranded DNA. HMCES acts at replication forks, binds PCNA and single-stranded DNA, and generates a DNA-protein crosslink to shield abasic sites from error-prone processing. This unusual HMCES DNA-protein crosslink intermediate is resolved by proteasome-mediated degradation. Acting as a suicide enzyme, HMCES prevents translesion DNA synthesis and the action of endonucleases that would otherwise generate mutations and double-strand breaks. HMCES is evolutionarily conserved in all domains of life, and its biochemical properties are shared with its E. coli ortholog. Thus, HMCES is an ancient DNA lesion recognition protein that preserves genome integrity by promoting error-free repair of abasic sites in single-stranded DNA.
Identifiants
pubmed: 30554877
pii: S0092-8674(18)31454-5
doi: 10.1016/j.cell.2018.10.055
pmc: PMC6329640
mid: NIHMS1511529
pii:
doi:
Substances chimiques
DNA, Single-Stranded
0
DNA-Binding Proteins
0
Polynucleotides
0
Proliferating Cell Nuclear Antigen
0
apyrimidinic acid
0
Apurinic Acid
11002-22-5
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
DNA
9007-49-2
Endonucleases
EC 3.1.-
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
Pagination
144-153.e13Subventions
Organisme : NCI NIH HHS
ID : T32 CA009582
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007347
Pays : United States
Organisme : NIGMS NIH HHS
ID : F32 GM126646
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA228242
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM116616
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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