Sequence and chromatin features guide DNA double-strand break resection initiation.
CtIP
DNA double-strand break
DNA repair
Mre11
Sae2
chromatin
homologous recombination
resection
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
20 04 2023
20 04 2023
Historique:
received:
03
06
2022
revised:
09
01
2023
accepted:
09
02
2023
pmc-release:
20
04
2024
medline:
25
4
2023
pubmed:
15
3
2023
entrez:
14
3
2023
Statut:
ppublish
Résumé
DNA double-strand breaks (DSBs) are cytotoxic genome lesions that must be accurately and efficiently repaired to ensure genome integrity. In yeast, the Mre11-Rad50-Xrs2 (MRX) complex nicks 5'-terminated DSB ends to initiate nucleolytic processing of DSBs for repair by homologous recombination. How MRX-DNA interactions support 5' strand-specific nicking and how nicking is influenced by the chromatin context have remained elusive. Using a deep sequencing-based assay, we mapped MRX nicks at single-nucleotide resolution next to multiple DSBs in the yeast genome. We observed that the DNA end-binding Ku70-Ku80 complex directed DSB-proximal nicks and that repetitive MRX cleavage extended the length of resection tracts. We identified a sequence motif and a DNA meltability profile that is preferentially nicked by MRX. Furthermore, we found that nucleosomes as well as transcription impeded MRX incisions. Our findings suggest that local DNA sequence and chromatin features shape the activity of this central DSB repair complex.
Identifiants
pubmed: 36917982
pii: S1097-2765(23)00113-2
doi: 10.1016/j.molcel.2023.02.010
pmc: PMC10131398
mid: NIHMS1876524
pii:
doi:
Substances chimiques
Chromatin
0
Saccharomyces cerevisiae Proteins
0
Endodeoxyribonucleases
EC 3.1.-
Exodeoxyribonucleases
EC 3.1.-
DNA
9007-49-2
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
1237-1250.e15Subventions
Organisme : NCI NIH HHS
ID : P01 CA174653
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM126997
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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