Abstract:
:TopBP1 is involved in DNA replication and DNA damage checkpoint. Recent studies have demonstrated that TopBP1 is a direct positive effecter of ATR. However, it is not known how TopBP1 recognizes damaged DNA. Here, we show that TopBP1 formed nuclear foci after exposure to ionizing radiation, but such TopBP1 foci were abolished in Nijmegen breakage syndrome cells. We also show that TopBP1 physically associated with NBS1 in vivo. These results suggested that NBS1 might regulate TopBP1 recruitment to the sites of DNA damage. TopBP1-depleted cells showed hypersensitivity to Mitomycin C and ionizing radiation, an increased frequency of sister-chromatid exchange level, and a reduced frequency of DNA double-strand break induced homologous recombination repair. Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Morishima K,Sakamoto S,Kobayashi J,Izumi H,Suda T,Matsumoto Y,Tauchi H,Ide H,Komatsu K,Matsuura Sdoi
10.1016/j.bbrc.2007.08.086subject
Has Abstractpub_date
2007-11-03 00:00:00pages
872-9issue
4eissn
0006-291Xissn
1090-2104pii
S0006-291X(07)01780-9journal_volume
362pub_type
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