REGULATOR OF HOMOLOGOUS RECOMBINATION IN EUKARYOTIC CELLS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在裂殖酵母和芽生酵母中，依赖于RAD52的同源重组(HR)受SRs2和Rqh1/Sgs1 DNA解旋酶的抗重组酶活性调节。通过对裂殖酵母中Srs2的功能分析，我们发现了一种新的带有游泳型锌指的HR蛋白SWS1。SWS1的失活抑制了srs2和rqh1突变体的遗传毒性敏感性，并挽救了srs2 rqh1细胞的活力。SWS1在与Rlp1和Rdl1重组的早期阶段发挥作用，Rlp1和Rdl1是两个与人类RAD51 Paralog XRCC2和RAD51D关系最近的RecA样蛋白。这一发现表明，XRCC2？RAD51D复合体在低等真核生物中是保守的。人类细胞中存在SWS1同源基因。它与RAD51D相关，去除其表达可减少RAD51病灶的数目。这些研究揭示了一条在真核细胞中启动和控制HR的保守途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rad52-dependent homologous recombination (HR) is regulated by the antirecombinase activities of Srs2 and Rqh1/Sgs1 DNA helicases in fission yeast and budding yeast. Functional analysis of Srs2 in Schizosaccharomyces pombe led us to the discovery of Sws1, a novel HR protein with a SWIM-type Zn finger. Inactivation of Sws1 suppresses the genotoxic sensitivity of srs2 and rqh1 mutants and rescues the inviability of srs2 rqh1 cells. Sws1 functions at an early step of recombination in a pro-recombinogenic complex with Rlp1 and Rdl1, two RecA-like proteins that are most closely related to the human Rad51 paralogs XRCC2 and RAD51D, respectively. This finding indicates that the XRCC2?RAD51D complex is conserved in lower eukaryotes. A SWS1 homolog exists in human cells. It associates with RAD51D and ablating its expression reduces the number of RAD51 foci. These studies unveil a conserved pathway for the initiation and control of HR in eukaryotic cells.