RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination.
DNA homologous recombination
RNA polymerase III
RNA-DNA hyrbid
dsDNA break repair
end resection
genomic instability
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
04 03 2021
04 03 2021
Historique:
received:
06
09
2019
revised:
24
09
2020
accepted:
26
01
2021
pubmed:
25
2
2021
medline:
15
9
2021
entrez:
24
2
2021
Statut:
ppublish
Résumé
End resection in homologous recombination (HR) and HR-mediated repair of DNA double-strand breaks (DSBs) removes several kilobases from 5' strands of DSBs, but 3' strands are exempted from degradation. The mechanism by which the 3' overhangs are protected has not been determined. Here, we established that the protection of 3' overhangs is achieved through the transient formation of RNA-DNA hybrids. The DNA strand in the hybrids is the 3' ssDNA overhang, while the RNA strand is newly synthesized. RNA polymerase III (RNAPIII) is responsible for synthesizing the RNA strand. Furthermore, RNAPIII is actively recruited to DSBs by the MRN complex. CtIP and MRN nuclease activity is required for initiating the RNAPIII-mediated RNA synthesis at DSBs. A reduced level of RNAPIII suppressed HR, and genetic loss > 30 bp increased at DSBs. Thus, RNAPIII is an essential HR factor, and the RNA-DNA hybrid is an essential repair intermediate for protecting the 3' overhangs in DSB repair.
Identifiants
pubmed: 33626331
pii: S0092-8674(21)00091-X
doi: 10.1016/j.cell.2021.01.048
pii:
doi:
Substances chimiques
MRE11 protein, human
0
Multiprotein Complexes
0
RNA
63231-63-0
POLR3G protein, human
EC 2.7.7.-
POLR3A protein, human
EC 2.7.7.6
RNA Polymerase III
EC 2.7.7.6
Endodeoxyribonucleases
EC 3.1.-
MRE11 Homologue Protein
EC 3.1.-
RBBP8 protein, human
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1314-1329.e10Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.