The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
24866
Cancer Research UK - United Kingdom
PubMed
38039132
DOI
10.1016/j.celrep.2023.113489
PII: S2211-1247(23)01501-2
Knihovny.cz E-zdroje
- Klíčová slova
- CP: Molecular biology, DNA damage, DNA:RNA hybrids, LLPS, R-loops, RNA polymerase II, SOSS1 complex, c-Abl kinase, hSSB1, phase-separation, phosphorylation,
- MeSH
- DNA vazebné proteiny * metabolismus MeSH
- oprava DNA MeSH
- poškození DNA MeSH
- RNA-polymerasa II * metabolismus MeSH
- separace fází MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny * MeSH
- RNA-polymerasa II * MeSH
Double-strand breaks (DSBs) are the most severe type of DNA damage. Previously, we demonstrated that RNA polymerase II (RNAPII) phosphorylated at the tyrosine 1 (Y1P) residue of its C-terminal domain (CTD) generates RNAs at DSBs. However, the regulation of transcription at DSBs remains enigmatic. Here, we show that the damage-activated tyrosine kinase c-Abl phosphorylates hSSB1, enabling its interaction with Y1P RNAPII at DSBs. Furthermore, the trimeric SOSS1 complex, consisting of hSSB1, INTS3, and c9orf80, binds to Y1P RNAPII in response to DNA damage in an R-loop-dependent manner. Specifically, hSSB1, as a part of the trimeric SOSS1 complex, exhibits a strong affinity for R-loops, even in the presence of replication protein A (RPA). Our in vitro and in vivo data reveal that the SOSS1 complex and RNAPII form dynamic liquid-like repair compartments at DSBs. Depletion of the SOSS1 complex impairs DNA repair, underscoring its biological role in the R-loop-dependent DNA damage response.
Central European Institute of Technology Masaryk University 62500 Brno Czech Republic
Sir William Dunn School of Pathology University of Oxford South Parks Road Oxford OX1 3RE UK
Citace poskytuje Crossref.org
Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks