The phosphorylated trimeric SOSS1 complex and RNA polymerase II
trigger liquid-liquid phase separation at double-strand breaks

J 2023

The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks

LONG, Qilin; Marek ŠEBESTA; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Adele ALAGIA et. al.

Základní údaje

Originální název

The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks

Autoři

LONG, Qilin; Marek ŠEBESTA (703 Slovensko, garant, domácí); Kateřina ŠEDOVÁ (203 Česká republika, domácí); Vojtěch HALUZA (203 Česká republika, domácí); Adele ALAGIA; Zhichao LIU; Richard ŠTEFL (203 Česká republika, domácí) a Monika GULLEROVA

Vydání

Cell Reports, Elsevier, 2023, 2211-1247

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.500

Kód RIV

RIV/00216224:14740/23:00133166

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1016/j.celrep.2023.113489

UT WoS

001127113200001

EID Scopus

2-s2.0-85178153659

Klíčová slova anglicky

c-Abl kinase; CP: Molecular biology; DNA damage; DNA:RNA hybrids; hSSB1; LLPS; phase-separation; phosphorylation; R-loops; RNA polymerase II; SOSS1 complex

Štítky

CF CELLIM, CF PROT, RNA4T

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 1. 2025 13:35, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

GM21-10464M, projekt VaV

Název: Strukturní charakterizace interakcí mezi transkripcí a opravou DNA

Investor: Grantová agentura ČR, Structural characterisation of the interplay between transcription and DNA repair

649030, interní kód MU

Název: DECOR - Dynamic assembly and exchange of RNA polymerase II CTD factors (Akronym: DECOR)

Investor: Evropská unie, DECOR - Dynamic assembly and exchange of RNA polymerase II CTD factors, ERC (Excellent Science)

90242, velká výzkumná infrastruktura

Název: CIISB III

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

90254, velká výzkumná infrastruktura

Název: e-INFRA CZ II

Přiložené soubory

1-s2.0-S2211124723015012-main.pdf

Citovat

LONG, Qilin; Marek ŠEBESTA; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Adele ALAGIA; Zhichao LIU; Richard ŠTEFL a Monika GULLEROVA. The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks. Cell Reports. Elsevier, 2023, roč. 42, č. 12, s. 1-25. ISSN 2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2023.113489.

@article{2364700,
   author = {Long, Qilin and Šebesta, Marek and Šedová, Kateřina and Haluza, Vojtěch and Alagia, Adele and Liu, Zhichao and Štefl, Richard and Gullerova, Monika},
   article_number = {12},
   doi = {https://doi.org/10.1016/j.celrep.2023.113489},
   keywords = {c-Abl kinase; CP: Molecular biology; DNA damage; DNA:RNA hybrids; hSSB1; LLPS; phase-separation; phosphorylation; R-loops; RNA polymerase II; SOSS1 complex},
   language = {eng},
   issn = {2211-1247},
   journal = {Cell Reports},
   title = {The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks},
   url = {https://www.sciencedirect.com/science/article/pii/S2211124723015012},
   volume = {42},
   year = {2023}
}

TY  - JOUR
ID  - 2364700
AU  - Long, Qilin - Šebesta, Marek - Šedová, Kateřina - Haluza, Vojtěch - Alagia, Adele - Liu, Zhichao - Štefl, Richard - Gullerova, Monika
PY  - 2023
TI  - The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks
JF  - Cell Reports
VL  - 42
IS  - 12
SP  - 1-25
EP  - 1-25
PB  - Elsevier
SN  - 22111247
KW  - c-Abl kinase
KW  - CP: Molecular biology
KW  - DNA damage
KW  - DNA:RNA hybrids
KW  - hSSB1
KW  - LLPS
KW  - phase-separation
KW  - phosphorylation
KW  - R-loops
KW  - RNA polymerase II
KW  - SOSS1 complex
UR  - https://www.sciencedirect.com/science/article/pii/S2211124723015012
N2  - 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.
ER  -

LONG, Qilin; Marek ŠEBESTA; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Adele ALAGIA; Zhichao LIU; Richard ŠTEFL a Monika GULLEROVA. The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks. \textit{Cell Reports}. Elsevier, 2023, roč.~42, č.~12, s.~1-25. ISSN~2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2023.113489.

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