RAD51 Inhibition Induces R-Loop Formation in Early G1 Phase of the Cell Cycle.
B02 inhibitor
G1 phase of the cell cycle
R-loop
RAD51
origin of replication
pre-replication complex
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Apr 2021
03 Apr 2021
Historique:
received:
28
02
2021
revised:
26
03
2021
accepted:
01
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
14
5
2021
Statut:
epublish
Résumé
R-loops are three-stranded structures generated by annealing of nascent transcripts to the template DNA strand, leaving the non-template DNA strand exposed as a single-stranded loop. Although R-loops play important roles in physiological processes such as regulation of gene expression, mitochondrial DNA replication, or immunoglobulin class switch recombination, dysregulation of the R-loop metabolism poses a threat to the stability of the genome. A previous study in yeast has shown that the homologous recombination machinery contributes to the formation of R-loops and associated chromosome instability. On the contrary, here, we demonstrate that depletion of the key homologous recombination factor, RAD51, as well as RAD51 inhibition by the B02 inhibitor did not prevent R-loop formation induced by the inhibition of spliceosome assembly in human cells. However, we noticed that treatment of cells with B02 resulted in RAD51-dependent accumulation of R-loops in an early G1 phase of the cell cycle accompanied by a decrease in the levels of chromatin-bound ORC2 protein, a component of the pre-replication complex, and an increase in DNA synthesis. Our results suggest that B02-induced R-loops might cause a premature origin firing.
Identifiants
pubmed: 33916766
pii: ijms22073740
doi: 10.3390/ijms22073740
pmc: PMC8038378
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
ORC2 protein, human
0
Origin Recognition Complex
0
DNA
9007-49-2
RAD51 protein, human
EC 2.7.7.-
Rad51 Recombinase
EC 2.7.7.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grantová Agentura České Republiky
ID : 19-07674S
Organisme : Grantová Agentura České Republiky
ID : 21-22593X
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