Widespread chromatin context-dependencies of DNA double-strand break repair proteins.
Nat Commun
; 15(1): 5334, 2024 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-38909016
ABSTRACT
DNA double-strand breaks are repaired by multiple pathways, including non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ). The balance of these pathways is dependent on the local chromatin context, but the underlying mechanisms are poorly understood. By combining knockout screening with a dual MMEJNHEJ reporter inserted in 19 different chromatin environments, we identified dozens of DNA repair proteins that modulate pathway balance dependent on the local chromatin state. Proteins that favor NHEJ mostly synergize with euchromatin, while proteins that favor MMEJ generally synergize with distinct types of heterochromatin. Examples of the former are BRCA2 and POLL, and of the latter the FANC complex and ATM. Moreover, in a diversity of human cancer types, loss of several of these proteins alters the distribution of pathway-specific mutations between heterochromatin and euchromatin. Together, these results uncover a complex network of proteins that regulate MMEJNHEJ balance in a chromatin context-dependent manner.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Heterocromatina
/
Eucromatina
/
Quebras de DNA de Cadeia Dupla
/
Reparo do DNA por Junção de Extremidades
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2024
Tipo de documento:
Article