期刊
BIOPHYSICAL JOURNAL
卷 121, 期 8, 页码 1493-1501出版社
CELL PRESS
DOI: 10.1016/j.bpj.2022.03.011
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类别
资金
- National Key R&D Program of China [2021YFA1601400]
- National Natural Science Foun-dation of China [11975283, U1632271]
- Heavy Ion Research Facility in Lanzhou (HIRFL)
The DNA damage response is a highly organized process in which the involvement of DNA damage response factors depends on their biochemical reactions with each other and chromatin. Through live-cell imaging combined with heavy ion microbeam irradiation, this study investigated the response of XRCC1 in localized DNA damage and found that its recruitment and dissociation dynamics differed between the G1 and G2 phase. Furthermore, fractionated irradiation led to accelerated dissociation at previous damage sites and immediate recycling of XRCC1 with higher recruitment efficiency.
The DNA damage response is a highly orchestrated process. The involvement of the DNA damage response factors in DNA damage response depends on their biochemical reactions with each other and with chromatin. Using online live-cell imaging combined with heavy ion microbeam irradiation, we studied the response of the scaffold protein X-ray repair cross-complementary protein 1 (XRCC1) at the localized DNA damage in charged particle irradiated HT1080 cells expressing XRCC1tagged RFP. The results showed that XRCC1 was recruited to the DNA damage with ultrafast kinetics in a poly ADP-ribose polymerase-dependent manner. The consecutive reaction model well explained the response of XRCC1 at ion hits, and we found that the XRCC1 recruitment was faster and dissociation was slower in the G2 phase than those in the G1 phase. The fractionated irradiation of the same cells resulted in accelerated dissociation at the previous damage sites, and the dissociated XRCC1 immediately recycled with a higher recruitment efficiency. Our data revealed XRCC1's new rescue mechanism and its high turnover in DNA damage response, which benefits our understanding of the biochemical mechanism in DNA damage response.
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