DOUBLE STRAND BREAK REPAIR AND RECOMBINATION

在人类和其他真核生物中，DSB的修复是 依赖于参与染色质结构、细胞周期的蛋白质 反应机制和断裂DNA末端的酶促重新连接。 参与断裂修复和细胞周期的基因内突变 对DNA链断裂的反应已被证明是导致 几种人类癌症，也与衰老过程有关。 我们的研究工作集中在遗传学上的DSB修复， 易处理的酿酒酵母 DNA中的许多基因 修复在人类和酵母之间是保守的。 我们已经调查 DSB修复的几个重要方面。 （一）分析 重组修复与非重组修复的相对贡献 重组末端连接; ii）损伤响应性的表征 细胞周期检查点和参与这些检查点的基因的鉴定 iii）研究DSB的修复途径， 在末端具有可选择的结构，即钝的，互补的， 修饰的或受损的末端;和iv）基因的系统分析 参与DNA链断裂的酶修复。结论 这项工作包括以下内容： 由RAD 52组DNA修复基因介导的重组。 只有DSB 具有互补末端的是用于末端连接的基底，这需要 yKU 70、yKU 80和RAD 50。 所有形式的DSB均诱导G2期阻滞， 该过程依赖于RAD 9和RAD 17。 基因参与后 DSB还需要复制修复，包括RAD 5和RAD 6 修复. 测试的所有类型的DSB诱导重组和非整倍体。

Summary of Work: In humans and other eukaryotes the repair of DSBs is dependent upon proteins involved in chromatin structure, cell cycle response mechanisms and the enzymatic rejoining of broken DNA ends. Mutations within genes involved in break repair and in cell cycle responses to DNA strand breaks have been shown to be responsible for several human cancers and have also been implicated in the aging process. Our research efforts have focused on DSB repair in the genetically tractable yeast Saccharomyces cerevisiae. Many genes involved in DNA repair are conserved between humans and yeast. We have investigated several important aspects of DSB repair. These include i) analysis of the relative contributions of recombinational repair versus non- recombinational end-joining; ii) characterization of damage-responsive cell cycle checkpoints and identification of genes participating in these processes; iii) investigation of repair pathways available for DSBs which have alternative structures at the ends, i.e. blunt, complementary, modified, or damaged termini; and iv) systematic analysis of genes involved in the enzymatic repair of DNA strand breaks. Conclusions of this work include the following: all DSBs can be repaired by recombination mediated by the RAD52 group of DNA repair genes. Only DSBs with complementary ends are substrates for end-joining, which requires yKU70, yKU80 and RAD50. All forms of DSBs induce G2-phase arrest and this process is dependent upon RAD9 and RAD17. Genes involved in post- replication repair, including RAD5 and RAD6, are also required for DSB repair. All types of DSBs tested induce recombination and aneuploidy.