Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N 2200, Denmark.
EMBO Rep. 2011 Jul 1;12(7):705-12. doi: 10.1038/embor.2011.99.
To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.
为了确定 DNA 损伤修复和检查点途径之间的关键联系，我们进行了 RNA 干扰筛选，以寻找电离辐射诱导的 G2 检查点的调节剂，结果发现了乳腺癌基因 BRCA2。当 BRCA2 的相互作用伙伴 PALB2 耗尽时，检查点也被废除。BRCA2 和 PALB2 的耗竭导致检查点过早废除，并更早地激活 AURORA A-PLK1 检查点恢复途径。这些结果表明，乳腺癌肿瘤抑制因子和同源重组修复蛋白 BRCA2 和 PALB2 是 DNA 损伤后 G2 检查点维持的主要调节剂。
