Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

Q. Long, K. Ajit, K. Sedova, V. Haluza, R. Stefl, S. Dokaneheifard, F. Beckedorff, MG. Valencia, M. Sebesta, R. Shiekhattar, M. Gullerova

. 2024 ; 52 (21) : 13036-13056. [pub] 20241127

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003378

Grantová podpora
R01GM078455 Sylvester Comprehensive Cancer Center
21-10464M Grant Agency of the Czech Republic
BVR01170 Cancer Research UK - United Kingdom
R01 GM078455 NIGMS NIH HHS - United States
649030 European Research Council - International
CZ.02.01.01/00/22_008/0004575 Ministry of Education
Lee Placito Fund
BVR01670 EPA Trust Fund
University of Oxford

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25003378
003      
CZ-PrNML
005      
20250206104314.0
007      
ta
008      
250121s2024 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gkae937 $2 doi
035    __
$a (PubMed)39445827
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Long, Qilin $u Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
245    10
$a Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks / $c Q. Long, K. Ajit, K. Sedova, V. Haluza, R. Stefl, S. Dokaneheifard, F. Beckedorff, MG. Valencia, M. Sebesta, R. Shiekhattar, M. Gullerova
520    9_
$a 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.
650    12
$a dvouřetězcové zlomy DNA $7 D053903
650    _2
$a lidé $7 D006801
650    12
$a RNA $x metabolismus $x genetika $x chemie $7 D012313
650    12
$a DNA $x metabolismus $x chemie $7 D004247
650    12
$a oprava DNA $7 D004260
650    12
$a RNA-polymerasa II $x metabolismus $7 D012319
650    _2
$a proteinfosfatasa 2 $x metabolismus $x genetika $7 D054648
650    _2
$a RNA-helikasy $x metabolismus $x genetika $7 D020365
650    _2
$a DNA-helikasy $x metabolismus $x genetika $7 D004265
650    _2
$a R-smyčka $7 D000080870
650    _2
$a fosforylace $7 D010766
650    _2
$a homeostáza $x genetika $7 D006706
650    _2
$a DNA vazebné proteiny $x metabolismus $7 D004268
655    _2
$a časopisecké články $7 D016428
700    1_
$a Ajit, Kamal $u Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
700    1_
$a Sedova, Katerina $u CEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic
700    1_
$a Haluza, Vojtech $u CEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic
700    1_
$a Stefl, Richard $u CEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic $u National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno CZ-62500, Czech Republic $1 https://orcid.org/0000000305585952 $7 mub2010582198
700    1_
$a Dokaneheifard, Sadat $u Department of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA
700    1_
$a Beckedorff, Felipe $u Department of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA $1 https://orcid.org/0000000167356851
700    1_
$a Valencia, Monica G $u Department of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA
700    1_
$a Sebesta, Marek $u CEITEC-Central European Institute of Technology, Masaryk University, Brno CZ-62500, Czech Republic $1 https://orcid.org/0000000195464921
700    1_
$a Shiekhattar, Ramin $u Department of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA
700    1_
$a Gullerova, Monika $u Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK $1 https://orcid.org/0000000245122779
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 52, č. 21 (2024), s. 13036-13056
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39445827 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250121 $b ABA008
991    __
$a 20250206104309 $b ABA008
999    __
$a ok $b bmc $g 2263262 $s 1239385
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 52 $c 21 $d 13036-13056 $e 20241127 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
GRA    __
$a R01GM078455 $p Sylvester Comprehensive Cancer Center
GRA    __
$a 21-10464M $p Grant Agency of the Czech Republic
GRA    __
$a BVR01170 $p Cancer Research UK $2 United Kingdom
GRA    __
$a R01 GM078455 $p NIGMS NIH HHS $2 United States
GRA    __
$a 649030 $p European Research Council $2 International
GRA    __
$a CZ.02.01.01/00/22_008/0004575 $p Ministry of Education
GRA    __
$p Lee Placito Fund
GRA    __
$a BVR01670 $p EPA Trust Fund
GRA    __
$p University of Oxford
LZP    __
$a Pubmed-20250121

Najít záznam

Citační ukazatele

Možnosti archivace