Widespread chromatin context-dependencies of DNA double-strand break repair proteins

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...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature communications Ročník 15; číslo 1; s. 5334 - 14
Hlavní autoři:	Vergara, Xabier, Manjón, Anna G., de Haas, Marcel, Morris, Ben, Schep, Ruben, Leemans, Christ, Friskes, Anoek, Beijersbergen, Roderick L., Sanders, Mathijs A., Medema, René H., van Steensel, Bas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 22.06.2024 Nature Publishing Group Nature Portfolio
Témata:	45/23 45/77 49 49/47 49/56 631/337/1427 631/553/2711 Ataxia Telangiectasia Mutated Proteins - genetics Ataxia Telangiectasia Mutated Proteins - metabolism BRCA2 protein BRCA2 Protein - genetics BRCA2 Protein - metabolism Breast cancer Chromatin Chromatin - genetics Chromatin - metabolism Context Deoxyribonucleic acid DNA DNA Breaks, Double-Stranded DNA damage DNA End-Joining Repair DNA Repair Double-strand break repair Euchromatin Euchromatin - genetics Euchromatin - metabolism Heterochromatin Heterochromatin - genetics Heterochromatin - metabolism Humanities and Social Sciences Humans multidisciplinary Non-homologous end joining Proteins Science Science (multidisciplinary) Synergism Yeast
ISSN:	2041-1723, 2041-1723
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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 MMEJ:NHEJ 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 MMEJ:NHEJ balance in a chromatin context-dependent manner. DNA double-strand breaks are repaired by multiple pathways. The balance of these pathways depends on the local chromatin context, but the underlying mechanisms are poorly understood. Here the authors uncover a network of proteins that regulate pathway balance in a chromatin context-dependent manner.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-49232-x