Role of Mei5-Sae3 in meiotic homologous recombination

Mei5-Sae3 在减数分裂同源重组中的作用

基本信息

批准号：
8680260
负责人：
Michael G. Sehorn
金额：
$ 23.19万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8680260
关键词：
Acute Myelocytic Leukemia Alkylating Agents Aneuploidy Binding Biochemical Biological Cells Charcot-Marie-Tooth Disease Chromatids Chromosomes Chronic Lymphocytic Leukemia Complex Cruciform DNA DNA DNA Binding DNA Double Strand Break DNA biosynthesis DNA replication fork DNA-Binding Proteins Development Disease Double Strand Break Repair Down Syndrome Dysmyelopoietic Syndromes Edward&apos s syndrome Embryo Etiology Failure Filament Foundations Gene Deletion Gene Duplication Genes Genetic Recombination Genome Goals Homologous Gene Human Invaded Investigation Ionizing radiation Lead Ligands Light Maintenance Malignant Neoplasms Mediating Mediator of activation protein Meiosis Meiotic Recombination Mental Retardation Mitotic Molecular Mutation Nucleoproteins Orthologous Gene Paralysed Pathway interactions Play Polyploidy Process Public Health Rad51 recombinase Radiation Role Single-Stranded DNA Sister Chromatid Site Spontaneous abortion Structure System Tail Testing Variant Work cancer cell defined contribution genetic analysis hereditary neuropathy homologous recombination human disease insight mutant neoplastic cell novel pressure presynaptic programs protein protein interaction recombinase repaired research study response yeast genetics

项目摘要

DESCRIPTION (provided by applicant): Meiosis is initiated by the programmed formation of DNA double strand breaks (DSBs). After the formation of the DSB, processing of the broken ends occurs to reveal single strand DNA that serves as the nucleation site for the homologous recombination machinery. Two RecA orthologs, Rad51 and Dmc1 cooperate to repair the DSBs in a manner that promotes chromosomal crossover formation between homologous chromatids rather than sister chromatids as in mitotic cells. This process is mediated by the Rad51 is present in both mitotic and meiotic cells while Dmc1 is specifically expressed in meiosis. Both Rad51 and Dmc1 nucleate on the single strand DNA (ssDNA) tails to form helical nucleoprotein filaments. Accessory factors known as recombination mediators promote the association of Rad51 and Dmc1 with the ssDNA. The Rad51 and Dmc1 nucleoprotein filaments invade the chromosomal homologue in search of homology. Once homology is found, a displacement loop forms followed by DNA strand exchange. The invading strand of the D-loop structure primes DNA synthesis while the second ssDNA tail is captured to form a Holliday junction. This linkage is important to keep the chromosomal homologs together until disjunction in Meiosis I. The Holliday junction is processed to form either crossovers or non-crossovers. Studies to date have unveiled only a recombination mediator activity of Mei5-Sae3 for the meiosis-specific Dmc1 recombinase. Herein, we outline strategies to determine the significance of novel protein-protein interactions involving the Mei5-Sae3 complex. In addition, we will define the contributions of the Mei5-Sae3-mediated DNA binding and protein-protein interactions in meiotic homologous recombination. The proposed studies will provide insight into the mechanism of meiotic recombination.

描述（由申请人提供）：减数分裂是由DNA双链断裂的编程形成（DSB）引发的。在形成DSB之后，发生破碎的末端的处理以揭示单链DNA，作为同源重组机制的成核位点。两个RECA直系同源物，Rad51和DMC1以促进同源染色单体之间的染色体交叉形成的方式进行修复DSB，而不是姐妹染色单体，如有丝分裂细胞。此过程是由RAD51介导的，在有丝分裂细胞和减数分裂细胞中均存在，而DMC1在减数分裂中特异性表达。 RAD51和DMC1在单链DNA（ssDNA）尾部有核，以形成螺旋核蛋白丝。被称为重组介质的辅助因子促进了RAD51和DMC1与ssDNA的关联。 RAD51和DMC1核蛋白丝侵入寻找同源性的染色体同源物。一旦找到同源性，会取代环形形式，然后是DNA链交换。 D-Loop结构的入侵链DNA合成，而第二sdna尾巴被捕获以形成Holliday结。这种连锁对于将染色体同源物保持在一起很重要，直到减数分裂I的分离I。Holliday连接被处理以形成跨界或非交叉。迄今为止，研究仅揭示了MEI5-SAE3的重组介质活性，用于减数分裂特异性DMC1重组酶。在此，我们概述了确定涉及MEI5-SAE3复合物的新型蛋白质蛋白相互作用的重要性的策略。此外，我们将定义MEI5-SAE3介导的DNA结合和蛋白质 - 蛋白质相互作用在减数分裂同源重组中的贡献。拟议的研究将洞悉减数分裂重组的机制。