Growth of IR-induced foci and G1 checkpoint

Motohiro Yamauchi, Keiji Suzuki, Seiji Kodama, Masami Watanabe

Research output: Contribution to journalArticlepeer-review

Abstract

It is well established that several checkpoint-, or repair factors, such as Ser1981-phosphorylated ATM protein, form discrete nuclear foci at the sites of DNA double-strand breaks (DSBs) caused by ionizing radiation (IR). The foci number decreases concurrently with DNA repair, but some fractions of the foci remain long after irradiation. While the mean size of the initial foci was approximately 0.6 μm in diameter 1 h after IR, the foci grew and the mean size reached ∼ 2.0 μm 24 h after irradiation. The percentage of cells with large foci, whose diameter is defined to be 1.6 μm or more, increased dose-dependently. All of the large foci of phosphorylated ataxia-telangiectasia mutated (ATM) colocalized with foci of Ser139-phosphorylated histone H2AX, mediator of DNA damage checkpoint (MDC)1, 53BP1 and Nijmegen breakage syndrome (NBS)1, which also grew similarly to phosphorylated ATM. When G0-synchronized cells were released soon after 1 Gy of X-rays, most of the cells with large phosphorylated ATM foci show no replication protein A (RPA) staining, which is the marker for the S phase cells, while RPA staining was frequently observed in cells with foci less than 1.6 μm in diameter. Furthermore, the percentage of cells with Ser15-phosphorylated p53 increased dependently on focus diameter of phosphorylated ATM, and more than 80% of the cells with large focus showed pan-nuclear staining of phosphorylated p53. These results indicate that the growth of IR-induced foci plays an essential role in amplifying DNA damage checkpoint signals in order to secure cells with a few residual DSBs or misrepaired DSBs against G1-S transition.

Original languageEnglish
Pages (from-to)235-238
Number of pages4
JournalInternational Congress Series
Volume1299
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Fingerprint Dive into the research topics of 'Growth of IR-induced foci and G1 checkpoint'. Together they form a unique fingerprint.

Cite this