DNA POLYMERASE STRUCTURES

这个子项目是许多研究子项目中的一个 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。列出的机构是 中心，不一定是研究者的机构。 真核生物DNA聚合酶<$（Pol <$）参与基因组复制、同源重组、DNA修复和损伤耐受。 人类Pol由四个亚基组成：p125，p50，p66和p12。最大的催化亚基含有聚合酶和3 '<$5'核酸外切酶活性位点结构域。辅助性p50、p66和p12亚基没有催化活性，它们被认为起调节作用，通过介导与PCNA的额外相互作用刺激p125的聚合酶活性，并稳定整个Pol？复合物。p50通过与所有其他三个亚基同时相互作用而充当Pol？组装的支架。 此外，p50还参与募集几种调节DNA代谢的蛋白质，包括p21、PDIP 1、PDIP 38、PDIP 46和WRN。 负责与p66、p125和p12相互作用的p50部分尚未确定。 使用双杂交筛选，人p66已被证明含有p50-和PCNA-结合结构域内的144 N-和20 C-末端氨基酸，分别。 有趣的是，Pol <$的许多基本功能，包括复制、TLS和BIR的调节，都是由p66亚基介导的，因此显然依赖于其p50和p66亚基之间的相互作用。 本课题的目的是研究p50亚基与人Pol？第三p66亚基N端144个氨基酸的复合物。

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. The eukaryotic DNA polymerase ¿ (Pol ¿) participates in genome replication, homologous recombination, DNA repair and damage tolerance. Human Pol ¿ consists of four subunits: p125, p50, p66, and p12. The largest catalytic subunit contains the polymerase and 3'¿5' exonuclease active sites domains. No catalytic activity is associated with the auxiliary p50, p66, and p12 subunits, and they are thought to play a regulatory role, stimulate the polymerase activity of p125 by mediating additional interactions with PCNA, and stabilize the entire Pol ¿ complex. p50 serves as a scaffold for the assembly of Pol ¿ by interacting simultaneously with all of the other three subunits. In addition, p50 is also involved in the recruitment of several proteins regulating DNA metabolism, including p21, PDIP1, PDIP38, PDIP46 and WRN. The parts of p50 responsible for interactions with p66, p125 and p12 have not been defined. Using two-hybrid screening, the human p66 has been shown to contain p50- and PCNA-binding domains within the 144 N- and 20 C-terminal amino acids, respectively. Interestingly, many essential functions of Pol ¿, including the regulation of replication, TLS and BIR, are mediated by the p66 subunit and thus apparently depend on the interaction between its p50 and p66 subunits. The goal of this subproject is to study the complex between the p50 subunit and the 144 amino acids N-terminal domain of the third p66 subunit (p66N) of human Pol ¿.