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

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。 Nbs1和Mre11分别与奈梅根破裂综合征(NBS)和共济失调-毛细血管扩张样疾病(ATLD)有关，受影响的患者容易患癌症。Mre11、Nbs1和Rad50形成一个保守的蛋白质复合体，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S期的复制控制、复制检查点和防止DSB的形成，但具体机制尚不清楚。我们建议研究mre11/Rad50/Nbs1复合体(MRN)在保持基因组完整性方面的关键作用，特别是在介导S期相关的DNA损伤反应方面的机制。

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.