p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
Abstract
This study aimed to explore a role of p21Waf1 in γH2AX foci formation and DNA repair as assessed by a Host-Cell Reactivation Assay in wild-type (p21Waf+/+) and p21Waf1-deficient E1A+Ras-transformed cells. p21Waf1+/+ cells have low γH2AX background compared to p21Waf1−/− cells. The treatment with histone deacetylase inhibitor (HDI) sodium butyrate (NaBut) causes to accumulation of γH2AX in p21Waf+/+ cells with little effect in p21Waf−/− cells. Moreover, NaBut inhibits DNA repair in wt cells but not in p21Waf1−/− cells. This could be explained by the weakening of GADD45 and PCNA proteins binding in NaBut-treated p21Waf1-expressing cells but not in p21Waf1−/− cells. We suggest that in wt-ERas cells NaBut activates both p21Waf1 expression and a release of p21Waf1 from the complexes with E1A that leads to suppression of DNA repair and promotes γH2AX persistency. The absence of p21Waf1 is by itself considered by the cell as stressful factor with formation of γH2AX. But the lack of p21Waf1 interferes with an inhibitory effect of NaBut to inhibit DNA repair and thereby to stop concomitant accumulation of harmful mutations. We conclude that p21Waf1 is directly involved in control of genome integrity and DNA repair acting through modulation of the components of the DNA repair machinery.
Funding source: Russian Science Foundation
Award Identifier / Grant number: 14-50-00068
Funding statement: Authors thank Dr. Chuxia Deng for a kind of CDKN1A-knockout mice. This work was supported by grant of the Russian Science Foundation (RSF), Funder Id: 10.13039/501100006769, No. 14-50-00068 and in part by Funder Id: 10.13039/501100002674, the Program ‘Molecular and Cell Biology’ of the Russian Academy of Sciences.
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Supplementary Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0249).
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk
- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
- Minireview
- Transcriptional regulation of human defense peptides: a new direction in infection control
- Research Articles/Short Communications
- Cell Biology and Signaling
- Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer
- p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway
Artikel in diesem Heft
- Frontmatter
- Reviews
- Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk
- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
- Minireview
- Transcriptional regulation of human defense peptides: a new direction in infection control
- Research Articles/Short Communications
- Cell Biology and Signaling
- Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer
- p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway