ROLE OF THE MRE11/RAD50/NBS1 COMPLEX IN DNA DAMAGE RESPONSE PATHWAYS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 Nbs 1和Mre 11分别与奈梅亨断裂综合征（NBS）和共济失调-毛细血管扩张样疾病（ATLD）相关，受影响的患者易患癌症。 Mre 11、Nbs 1和Rad 50形成了一个保守的蛋白质复合物，这是维持基因组稳定性所必需的。 最近的研究也发现了MRN在S期相关事件中的新作用，如复制控制、复制检查点和阻止S期DSB的形成，但具体机制尚不清楚。 我们建议调查的Mre 11/Rad 50/Nbs 1复合物（MRN）在保持基因组的完整性，特别是在介导S期相关的DNA损伤反应的关键作用的机制。

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. Nbs1 and Mre11 are linked to the Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD), respectively, and the affected patients are predisposed to cancer. Mre11, Nbs1 and Rad50 form a conserved protein complex that is required for the maintenance of genome stability. Recent studies have also uncovered new roles of MRN in S-phase related events, such as replication control, replication checkpoint and prevention of DSB formation in S-phase, but detailed mechanisms are not clear. We propose to investigate the mechanisms underlying the critical roles of the Mre11/Rad50/Nbs1 complex (MRN) in preserving genome integrity, especially in mediating S-phase-associated DNA damage responses.