Aylon Yael, Kupiec Martin
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Mol Cell Biol. 2003 Sep;23(18):6585-96. doi: 10.1128/MCB.23.18.6585-6596.2003.
Upon chromosomal damage, cells activate a checkpoint response that includes cell cycle arrest and a stimulation of DNA repair. The checkpoint protein Rad24 is key to the survival of a single, repairable double-strand break (DSB). However, the low survival of rad24 cells is not due to their inability to arrest cell cycle progression. In rad24 mutants, processing of the broken ends is delayed and protracted, resulting in extended kinetics of DSB repair and in cell death. The limited resection of rad24 mutants also affects recombination partner choice by a mechanism dependent on the length of the interacting homologous donor sequences. Unexpectedly, rad24 cells with a DSB eventually accumulate and die at the G(2)/M phase of the cell cycle. This arrest depends on the spindle checkpoint protein Mad2.
在染色体受损时,细胞会激活一种检查点反应,包括细胞周期停滞和对DNA修复的刺激。检查点蛋白Rad24对于单个可修复双链断裂(DSB)的存活至关重要。然而,rad24细胞的低存活率并非由于它们无法阻止细胞周期进程。在rad24突变体中,断裂末端的处理被延迟且延长,导致DSB修复动力学延长并导致细胞死亡。rad24突变体有限的切除也通过一种依赖于相互作用的同源供体序列长度的机制影响重组伙伴的选择。出乎意料的是,具有DSB的rad24细胞最终会在细胞周期的G(2)/M期积累并死亡。这种停滞取决于纺锤体检查点蛋白Mad2。