FUNCTIONAL STUDIES OF THE MEIOTIC MUTS HOMOLOGS HMSH4-HM

描述：(改编自申请者的摘要)Muts家族 同系物似乎共同发挥腺苷核苷酸调节作用 分子开关，发出DNA和细胞过程的时间信号 作为错配修复以及在压倒性DNA事件中的细胞凋亡 损坏。异二聚体MutS同系物hMSH4-hMSH5似乎具有独特的功能 在减数分裂细胞中。此外，有丝分裂的精原细胞向 初级精母细胞在减数分裂中的表达I揭示了从 HMSH2转化为hMSH5的表达。这项研究提案的目的是 从生化、分子和遗传学角度研究hMSH4-hMSH5的功能 方法论。 他们建议：1)刻画功能和功能域 HMSH4和hMSH5及其异二聚体形式hMSH4-hMSH5，2)确定 HMSH4-hMSH5与人异二聚体的功能相互作用(S) MutL同系物，3)确定hMSH4-hMSH5之间的功能相互作用(S) 和几个人类RecA同源物和重组相关蛋白，4) HMSH4-hMSH5蛋白的生化特性；包括DNA结合 和ATPase活性，以及5)DNA结构的描绘(S) HMSH4-hMSH5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.