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.

Basic information

Original name

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

Authors

LONG, Qilin; Marek ŠEBESTA (703 Slovakia, guarantor, belonging to the institution); Kateřina ŠEDOVÁ (203 Czech Republic, belonging to the institution); Vojtěch HALUZA (203 Czech Republic, belonging to the institution); Adele ALAGIA; Zhichao LIU; Richard ŠTEFL (203 Czech Republic, belonging to the institution) and Monika GULLEROVA

Edition

Cell Reports, Elsevier, 2023, 2211-1247

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 7.500

RIV identification code

RIV/00216224:14740/23:00133166

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

001127113200001

EID Scopus

2-s2.0-85178153659

Keywords in English

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

Abstract

In the original language

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.

Links

EF18_046/0015974, research and development project

Name: Modernizace České infrastruktury pro integrativní strukturní biologii

GM21-10464M, research and development project

Name: Strukturní charakterizace interakcí mezi transkripcí a opravou DNA

Investor: Czech Science Foundation

649030, interní kód MU

Name: DECOR - Dynamic assembly and exchange of RNA polymerase II CTD factors (Acronym: DECOR)

Investor: European Union, DECOR, ERC (Excellent Science)

90242, large research infrastructures

Name: CIISB III

90250, large research infrastructures

Name: Czech-BioImaging III

90254, large research infrastructures

Name: e-INFRA CZ II

Files attached

1-s2.0-S2211124723015012-main.pdf

Cite

LONG, Qilin; Marek ŠEBESTA; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Adele ALAGIA; Zhichao LIU; Richard ŠTEFL and Monika GULLEROVA. The phosphorylated trimeric SOSS1 complex and RNA polymerase II trigger liquid-liquid phase separation at double-strand breaks. Cell Reports. Elsevier, 2023, vol. 42, No 12, p. 1-25. ISSN 2211-1247. Available from: 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 and 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, vol.~42, No~12, p.~1-25. ISSN~2211-1247. Available from: https://doi.org/10.1016/j.celrep.2023.113489.

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