Dataset Information

ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.

ABSTRACT: The ATR protein kinase has well-described roles in maintaining genomic integrity during the DNA synthesis phase of the cell cycle. However, ATR function in cells that are not actively replicating DNA remains largely unexplored. Using HaCaT and telomerase-immortalized human keratinocytes maintained in a confluent, nonreplicating state in vitro, ATR was found to be robustly activated in response to UVB radiation in a manner dependent on the nucleotide excision repair factor and DNA translocase XPB. Inhibition of ATR kinase activity under these conditions negatively impacted acute cell survival and cytotoxicity and severely inhibited the ability of UVB-irradiated HaCaT keratinocytes to proliferate upon stimulation with growth factors. Furthermore, ATR kinase inhibition in quiescent HaCaT keratinocytes potentiated UVB mutagenesis at the hypoxanthine phosphoribosyltransferase locus. Though ATR inhibition did not impact the rate of removal of cyclobutane pyrimidine dimers from genomic DNA, elevated levels of PCNA mono-ubiquitination and chromatin-associated PCNA and RPA indicate that excision gap-filling synthesis was altered in the absence of ATR signaling. These results indicate that the ATR kinase plays important roles in preventing mutagenesis and in promoting the proliferative potential of quiescent keratinocytes exposed to UVB radiation.

SUBMITTER: Shaj K

PROVIDER: S-EPMC6980238 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.

Shaj Kavya K Hutcherson Rebekah J RJ Kemp Michael G MG

Photochemistry and photobiology 20191017 1

The ATR protein kinase has well-described roles in maintaining genomic integrity during the DNA synthesis phase of the cell cycle. However, ATR function in cells that are not actively replicating DNA remains largely unexplored. Using HaCaT and telomerase-immortalized human keratinocytes maintained in a confluent, nonreplicating state in vitro, ATR was found to be robustly activated in response to UVB radiation in a manner dependent on the nucleotide excision repair factor and DNA translocase XPB ...[more]

PMID: 31554014

Similar Datasets

Project description:Phaseolus angularis L. is widely cultivated and is considered a superfood because of its nutritious protein and starch contents. Nevertheless, P. angularis’s effects on skin photoaging are unknown. The aim of this study was to research the effects of P. angularis seed extract (PASE) on photoaging in human keratinocytes (HaCaT) damaged by UVB radiation so as to find out whether PASE can be used as an effective anti-photoaging ingredient in cosmetic products. The antioxidant activities were assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical scavenging, and reactive oxygen species (ROS) assays. Enzyme-linked immunosorbent assay (ELISA) analysis was used to determine the change in matrix metalloproteinase (MMP)-1, and MMP-3. The protein levels of mitogen-activated protein kinase (MAPK)/activator protein (AP)-1, transforming growth factor beta (TGF)-β/suppressor of mothers against decapentaplegic (Smad), and NF-E2-related factor (Nrf)2/antioxidant response element (ARE) were measured by western blot. As a result, PASE increased DPPH and ABTS antioxidant activities in a dose-dependent manner. Additionally, PASE treatment (100 µg/mL) significantly reverted the damage induced by UVB (125 mJ/cm2) irradiation by downregulating ROS, matrix metalloproteinase (MMP)-1, and MMP-3 secretion and expression and increasing procollagen type I production. To suppress MMP-1 and MMP-3 secretion, PASE significantly decreased UVB-induced p38 and JNK phosphorylation and phosphorylated c-Fos and c-Jun nuclear translocation. PASE promoted collagen I production by inhibiting UVB-induced TGF-β activation and Smad7 overexpression; antioxidant properties also arose from the stimulation of the Nrf2-dependent expression of the antioxidant enzymes heme oxygenase (HO)-1 and quinone oxidoreductase (NQO)-1. Our data demonstrated that PASE has the potential to prevent ROS formation induced by UVB exposure by targeting specific pathways. Thus, PASE might be a potent anti-photoaging component to exploit in developing anti-aging products.

Dataset Information

ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.

Publications

ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets