| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Outline of Final Research Achievements |
In this study, we found that BARD1 interacts with Lys9-dimethylated histone H3 (H3K9me2) after DNA damage in an ATM-dependent but RNF168-independent manner. This interaction is mediated by HP1-gamma. A conserved HP1-binding motif in the BARD1 BRCT domain directly interacts with the chromoshadow domain of HP1 in vitro; mutations in this motif disrupt the retention of BRCA1/BARD1 at DNA double-strand break (DSB) sites. The inhibition of BARD1-HP1 interaction also inhibits accumulation of CtIP, FANCJ and RAD51 at DSB sites, suppressed damage-induced sister chromatid exchange, and allow ectopic accumulation of RIF1, an effector of non-homologous end joining, at the damaged loci in S-phase. The results indicate that the BARD1-HP1 interaction is critical to mediate homologous recombination repair of DSB.
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