In this study, we tried to clarify the nucleotide excision repair (NER)-related DNA structure(s) activating the signal transduction pathways and their biological impacts. We found that, under the quiescent condition, DSB (DNA double-strand break) is generated in an NER-dependent manner, in addition to the predicted single-stranded regions. In NER-proficient cells arrested in G0 phase, UV exposure activates ATM signaling pathway, which leads to the accumulation of DSV-related factors. Importantly, A-T cells are more sensitive to UV compared with normal cells when exposed under quiescent but not exponentially growing condition. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in peripheral T lymphocytes and hematopoietic stem cells from mice. These all results suggest that in vivo quiescent cells may suffer from the mixed types of DNA lesions such as ssDNA gaps and DSB after UV or chemical exposure generating NER substrates.
休止期においてNER依存的に活性化するDNA損傷応答機構の解析
.png)
PH-PR-WAKASUGI-M-kaken 2015-5p.pdf
(386.83KB)
