FUNCTIONAL STUDIES OF THE MEIOTIC MUTS HOMOLOGS HMSH4-HM

描述：（改编自申请人的摘要）MutS家族 同源物似乎共同起腺苷核苷酸调节作用， 分子开关，它发出DNA和细胞过程的信号， 错配修复以及细胞凋亡， 损害异二聚体MutS同源物hMSH 4-hMSH 5似乎具有独特的功能 在减数分裂细胞中。此外，从有丝分裂的精原细胞到 初级精母细胞在减数分裂I揭示了一个过渡的表达， hMSH 2对hMSH 5表达的影响。本研究提案的目标是 从生物化学、分子生物学和遗传学的角度研究hMSH 4-hMSH 5的功能 方法论。 他们建议：1）表征的功能和功能域的 hMSH 4和hMSH 5以及它们异二聚体形式hMSH 4-hMSH 5，2）确定 hMSH 4-hMSH 5与异二聚体人 MutL同源物，3）确定hMSH 4-hMSH 5之间的功能性相互作用 以及几种人RecA同源物和重组相关蛋白，4） hMSH 4-hMSH 5蛋白的生化表征;包括DNA结合 和ATP酶活性，以及5）描绘引起 通过hMSH 4-hMSH 5的ADP-ATP交换。

DESCRIPTION: (Adapted from the applicant's abstract) The family of MutS homologs appear to collectively function as adenosine nucleotide regulated molecular switches which signal the timing of DNA and cellular processes such as mismatch repair as well as apoptosis in the event of overwhelming DNA damage. The heterodimeric MutS homologs hMSH4-hMSH5 appear to function uniquely in meiotic cells. Moreover, the transition from mitotic spermatogonia to primary spermatocytes in Meiosis I reveal a transition from the expression of hMSH2 to the expression of hMSH5. It is the goal of this research proposal to examine the function of hMSH4-hMSH5 using biochemical, molecular and genetic methodologies. They propose to: 1) characterize the functions and functional domains of hMSH4 and hMSH5 as well as their heterodimeric form hMSH4-hMSH5, 2) determine the functional interaction(s) between hMSH4-hMSH5 and the heterodimeric human MutL homologs, 3) determine the functional interaction(s) between hMSH4-hMSH5 and several human RecA homologs and recombination associated proteins, 4) biochemical characterization of the hMSH4-hMSH5 protein; including DNA binding and ATPase activities, and 5) delineation of the DNA structure(s) that provokes ADP-ATP exchange by hMSH4-hMSH5.