• Je něco špatně v tomto záznamu ?

DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells

B. Boleslavska, A. Oravetzova, K. Shukla, Z. Nascakova, ON. Ibini, Z. Hasanova, M. Andrs, R. Kanagaraj, J. Dobrovolna, P. Janscak

. 2022 ; 50 (21) : 12274-12290. [pub] 2022Nov28

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22032566

R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81-LIG4-ELL pathway for resolution of R-loop-mediated transcription-replication conflicts, which may be involved in R-loop unwinding.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22032566
003      
CZ-PrNML
005      
20230131150711.0
007      
ta
008      
230120s2022 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gkac1116 $2 doi
035    __
$a (PubMed)36453994
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Boleslavska, Barbora $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $u Faculty of Science, Charles University in Prague, Albertov 6, 128 00 Prague 2, Czech Republic $1 https://orcid.org/0000000253366829
245    10
$a DDX17 helicase promotes resolution of R-loop-mediated transcription-replication conflicts in human cells / $c B. Boleslavska, A. Oravetzova, K. Shukla, Z. Nascakova, ON. Ibini, Z. Hasanova, M. Andrs, R. Kanagaraj, J. Dobrovolna, P. Janscak
520    9_
$a R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81-LIG4-ELL pathway for resolution of R-loop-mediated transcription-replication conflicts, which may be involved in R-loop unwinding.
650    _2
$a lidé $7 D006801
650    12
$a R-smyčka $7 D000080870
650    12
$a replikace DNA $x genetika $7 D004261
650    _2
$a DNA-helikasy $x metabolismus $7 D004265
650    _2
$a endonukleasy $x metabolismus $7 D004720
650    _2
$a DNA $x metabolismus $7 D004247
650    _2
$a DEAD-box RNA-helikasy $x genetika $x metabolismus $7 D053487
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Oravetzova, Anna $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $u Faculty of Science, Charles University in Prague, Albertov 6, 128 00 Prague 2, Czech Republic $1 https://orcid.org/0000000324833739
700    1_
$a Shukla, Kaustubh $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $1 https://orcid.org/0000000179214519
700    1_
$a Nascakova, Zuzana $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $1 https://orcid.org/0000000320358061
700    1_
$a Ibini, Oluwakemi Ngozi $u School of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK $1 https://orcid.org/0000000290782012
700    1_
$a Hasanova, Zdenka $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $1 https://orcid.org/0000000160471937
700    1_
$a Andrs, Martin $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $1 https://orcid.org/0000000258501567
700    1_
$a Kanagaraj, Radhakrishnan $u School of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK $u School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK $u Centre for Drug Discovery and Development, Sathyabama Institute of Science and Technology, Chennai 600119, India $1 https://orcid.org/0000000309065399
700    1_
$a Dobrovolna, Jana $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $1 https://orcid.org/0000000324122080
700    1_
$a Janscak, Pavel $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0000000217487789
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 50, č. 21 (2022), s. 12274-12290
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36453994 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230120 $b ABA008
991    __
$a 20230131150707 $b ABA008
999    __
$a ok $b bmc $g 1891377 $s 1183901
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2022 $b 50 $c 21 $d 12274-12290 $e 2022Nov28 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20230120
Zpět

Najít záznam

Citační ukazatele

    Možnosti archivace