Disruption of Chromatin Dynamics by Hypotonic Stress Suppresses HR and Shifts DSB Processing to Error-Prone SSA.
Ataxia Telangiectasia Mutated Proteins
/ genetics
Cell Cycle Checkpoints
/ drug effects
Cell Line
Cell Proliferation
/ drug effects
Chromatin
/ chemistry
DNA Breaks, Double-Stranded
/ radiation effects
DNA End-Joining Repair
/ drug effects
Histones
/ metabolism
Homologous Recombination
/ drug effects
Humans
Hypotonic Solutions
/ chemistry
RNA Interference
RNA, Small Interfering
/ metabolism
Rad52 DNA Repair and Recombination Protein
/ antagonists & inhibitors
Radiation, Ionizing
DNA double-strand breaks
DNA-damage-response
alternative end-joining (alt-EJ)
chromatin
chromatin dynamics
homologous recombination (HR)
hypotonic stress (HypoS)
ionizing radiation (IR)
nonhomologous end-joining (NHEJ)
single-strand annealing (SSA)
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:
11 Oct 2021
11 Oct 2021
Historique:
received:
24
08
2021
revised:
04
10
2021
accepted:
05
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The processing of DNA double-strand breaks (DSBs) depends on the dynamic characteristics of chromatin. To investigate how abrupt changes in chromatin compaction alter these dynamics and affect DSB processing and repair, we exposed irradiated cells to hypotonic stress (HypoS). Densitometric and chromosome-length analyses show that HypoS transiently decompacts chromatin without inducing histone modifications known from regulated local chromatin decondensation, or changes in Micrococcal Nuclease (MNase) sensitivity. HypoS leaves undisturbed initial stages of DNA-damage-response (DDR), such as radiation-induced ATM activation and H2AX-phosphorylation. However, detection of ATM-pS1981, γ-H2AX and 53BP1 foci is reduced in a protein, cell cycle phase and cell line dependent manner; likely secondary to chromatin decompaction that disrupts the focal organization of DDR proteins. While HypoS only exerts small effects on classical nonhomologous end-joining (c-NHEJ) and alternative end-joining (alt-EJ), it markedly suppresses homologous recombination (HR) without affecting DNA end-resection at DSBs, and clearly enhances single-strand annealing (SSA). These shifts in pathway engagement are accompanied by decreases in HR-dependent chromatid-break repair in the G
Identifiants
pubmed: 34681628
pii: ijms222010957
doi: 10.3390/ijms222010957
pmc: PMC8535785
pii:
doi:
Substances chimiques
Chromatin
0
H2AX protein, human
0
Histones
0
Hypotonic Solutions
0
RAD52 protein, human
0
RNA, Small Interfering
0
Rad52 DNA Repair and Recombination Protein
0
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bundesministerium für Bildung und Forschung
ID : 02NUK037B
Organisme : Bundesministerium für Bildung und Forschung
ID : 02NUK043B
Organisme : Bundesministerium für Bildung und Forschung
ID : 02NUK054B
Organisme : Deutsche Forschungsgemeinschaft
ID : GRK1739
Organisme : Bundesministerium für Wirtschaft und Energie
ID : 50WB1836
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