Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid
autoregulation at double-strand breaks

CSLog in Log in (EduId)

Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks

Přehled o publikaci

J 2024

Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks

LONG, Qilin; Kamal AJIT; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Richard ŠTEFL et. al.

Basic information

Original name

Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks

Authors

LONG, Qilin; Kamal AJIT; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Richard ŠTEFL; Sadat DOKANEHEIFARD; Felipe BECKEDORFF; Monica G. VALENCIA; Marek ŠEBESTA; Ramin SHIEKHATTAR and Monika GULLEROVA

Edition

Nucleic Acids Research, Oxford, Oxford University Press, 2024, 0305-1048

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Středoevropský technologický institut – Repository – Repository

DOI

http://dx.doi.org/10.1093/nar/gkae937

UT WoS

001340784500001

EID Scopus

2-s2.0-85211392890

Keywords in English

TRANSCRIPTIONAL PAUSE SITES; RNA-POLYMERASE-II; R-LOOPS; DAMAGE RESPONSE; REPAIR; INTEGRATOR; SENATAXIN; RECOMBINATION; PARTICIPATE; RECRUITMENT

Links

EH22_008/0004575, research and development project. GM21-10464M, research and development project. 649030, interní kód Repo.

Changed: 8/1/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids / R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair.

Files attached

https://is.muni.cz/publication/2465588/gkae937.pdf

Cite

LONG, Qilin; Kamal AJIT; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Richard ŠTEFL; Sadat DOKANEHEIFARD; Felipe BECKEDORFF; Monica G. VALENCIA; Marek ŠEBESTA; Ramin SHIEKHATTAR and Monika GULLEROVA. Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks. Nucleic Acids Research. Oxford: Oxford University Press, 2024, vol. 52, No 21, p. 13036-13056. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkae937.

@article{66252,
   author = {Long, Qilin and Ajit, Kamal and Šedová, Kateřina and Haluza, Vojtěch and Štefl, Richard and Dokaneheifard, Sadat and Beckedorff, Felipe and Valencia, Monica G. and Šebesta, Marek and Shiekhattar, Ramin and Gullerova, Monika},
   article_location = {Oxford},
   article_number = {21},
   doi = {http://dx.doi.org/10.1093/nar/gkae937},
   keywords = {TRANSCRIPTIONAL PAUSE SITES; RNA-POLYMERASE-II; R-LOOPS; DAMAGE RESPONSE; REPAIR; INTEGRATOR; SENATAXIN; RECOMBINATION; PARTICIPATE; RECRUITMENT},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks},
   url = {https://academic.oup.com/nar/article/52/21/13036/7833680?login=true},
   volume = {52},
   year = {2024}
}

TY  - JOUR
ID  - 66252
AU  - Long, Qilin - Ajit, Kamal - Šedová, Kateřina - Haluza, Vojtěch - Štefl, Richard - Dokaneheifard, Sadat - Beckedorff, Felipe - Valencia, Monica G. - Šebesta, Marek - Shiekhattar, Ramin - Gullerova, Monika
PY  - 2024
TI  - Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks
JF  - Nucleic Acids Research
VL  - 52
IS  - 21
SP  - 13036-13056
EP  - 13036-13056
PB  - Oxford University Press
SN  - 0305-1048
KW  - TRANSCRIPTIONAL PAUSE SITES
KW  - RNA-POLYMERASE-II
KW  - R-LOOPS
KW  - DAMAGE RESPONSE
KW  - REPAIR
KW  - INTEGRATOR
KW  - SENATAXIN
KW  - RECOMBINATION
KW  - PARTICIPATE
KW  - RECRUITMENT
UR  - https://academic.oup.com/nar/article/52/21/13036/7833680?login=true
N2  - DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids / R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair.
ER  -

LONG, Qilin; Kamal AJIT; Kateřina ŠEDOVÁ; Vojtěch HALUZA; Richard ŠTEFL; Sadat DOKANEHEIFARD; Felipe BECKEDORFF; Monica G. VALENCIA; Marek ŠEBESTA; Ramin SHIEKHATTAR and Monika GULLEROVA. Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2024, vol.~52, No~21, p.~13036-13056. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkae937.