DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 06 2020
22 06 2020
Historique:
received:
15
10
2019
accepted:
29
05
2020
entrez:
24
6
2020
pubmed:
24
6
2020
medline:
29
8
2020
Statut:
epublish
Résumé
Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR), which includes phosphorylation of histone H2Ax, forming γH2Ax. This histone modification spreads beyond the DSB into neighboring chromatin, generating a DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms that determine the breadth and intensity of γH2Ax domains remain unclear. Here, we show that chromosomal contacts of a DSB site are the primary determinants for γH2Ax landscapes. DSBs that disrupt a topological border permit extension of γH2Ax domains into both adjacent compartments. In contrast, DSBs near a border produce highly asymmetric DDR platforms, with γH2Ax nearly absent from one broken end. Collectively, our findings lend insights into a basic DNA repair mechanism and how the precise location of a DSB may influence genome integrity.
Identifiants
pubmed: 32572033
doi: 10.1038/s41467-020-16926-x
pii: 10.1038/s41467-020-16926-x
pmc: PMC7308414
doi:
Substances chimiques
Chromatin
0
H2AX protein, mouse
0
Histones
0
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
3158Subventions
Organisme : NCI NIH HHS
ID : R01 CA188286
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118852
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106697
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI102946
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI074953
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130231
Pays : United States
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