ATR/Chk1 pathway is activated by oxidative stress in response to UVA light in human Xeroderma Pigmentosum Variant cells.
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2019
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The crucial role of DNA polymerase eta in protecting against
sunlight-induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP-V) patients, who carry mutations in this
protein and present increased frequency of skin cancer. XPV cellular phenotypes may be aggravated if proteins of DNA
damage response (DDR) pathway are blocked, as widely
demonstrated by experiments with UVC light and caffeine.
However, little is known about the participation of DDR in
XP-V cells exposed to UVA light, the wavelengths patients
are mostly exposed. Here, we demonstrate the participation
of ATR kinase in protecting XP-V cells after receiving low
UVA doses using a specific inhibitor, with a remarkable
increase in sensitivity and cH2AX signaling. Corroborating
ATR participation in UVA-DDR, a significant increase in
Chk1 protein phosphorylation, as well as S-phase cell cycle
arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N-acetylcysteine (NAC), which significantly protects XP-V cells from
UVA light, even in the presence of the ATR inhibitor. These
findings indicate that the ATR/Chk1 pathway is activated to
control UVA-induced oxidatively generated DNA damage
and emphasizes the role of ATR kinase as a mediator of
genomic stability in pol eta defective cells.
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MORENO, N. C. et al. ATR/Chk1 pathway is activated by oxidative stress in response to UVA light in human Xeroderma Pigmentosum Variant cells. Photochemistry and Photobiology, v. 95, n. 1, p. 345-354, jan./fev. 2019. Disponível em: <https://onlinelibrary.wiley.com/doi/full/10.1111/php.13041>. Acesso em: 22 fev. 2019.