PROTEIN PHOSPHATASES AND DNA DAMAGE CHECKPOINT RECOVERY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我的实验室对DNA损伤反应（DDR）和细胞周期调控感兴趣。重要的是，这些通路的失调已被证明是癌症进展的因果因素，也是癌症治疗选择和结果的重要决定因素。我们的长期目标是描绘这些通路的潜在机制，并直接研究它们与人类癌症的联系。为了实现这一目标，我们结合联合收割机在体外，在非洲爪蟾卵提取物的功能研究在哺乳动物系统中，以揭示这些过程的新见解。 最近的研究表明，许多Ser/Thr磷酸酶复合物参与DDR调节。然而，人们对这一机制和规则知之甚少。有趣的是，DDR磷酸酶可能与癌症密切相关，如DDR激酶。我们希望通过体外和体内方法直接评估他们的癌症参与。我们研究的另一个主要兴趣是DNA损伤的细胞恢复过程。DNA修复完成后，恢复过程使DDR失活，使细胞恢复正常的细胞周期进程。这是决定DNA损伤或化疗后细胞命运的重要过程。然而，与复员方案的启动相比，对恢复机制的了解较少。我们已经开发了爪蟾卵提取物作为一个实验系统，系统地研究这一过程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. My lab is interested in the DNA damage response (DDR) and cell cycle regulation. Importantly, dysregulation of these pathways has been proven to be a causal factor in cancer progression, and an important determinant of treatment choice and outcome for cancer. Our long-term goal is to delineate the underlying mechanisms of these pathways, and to directly investigate their connection with human cancer. To achieve the goal, we combine in vitro, reconstitutive studies in Xenopus egg extracts with functional investigations in mammalian systems to reveal new insights into these processes. Recent studies revealed a number of Ser/Thr phosphatase complexes involved in DDR regulation. However, little is known about the mechanism and regulation. Interestingly, the DDR phosphatases may be tightly related to cancer, like DDR kinases. We hope to directly assess their cancer involvement through both in vitro and in vivo approaches. Another major interest of our research is the cellular recovery process from DNA damage. Upon completion of DNA repair, the recovery process de-activates the DDR, allowing the cell to return to normal cell cycle progression. This is an important process that determines cell fate post DNA damage or chemotherapy. However, compared to activation of the DDR, the recovery mechanism is less understood. We have developed Xenopus egg extracts as an experimental system to systematically investigate this process.