REGULATION OF MEIOTIC DEVELOPMENT BY MTS1-MTS2 PROTEIN

MTS1-MTS2 蛋白对减数分裂发育的调节

• 批准号: 6682384
• 负责人: Wayne P Wahls
• 金额: $ 12.81万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682384
• 关键词: Schizosaccharomyces pombe; acyltransferase; cell cycle; fungal genetics; genetic recombination; mitogen activated protein kinase; protein kinase A; transcription factor

DESCRIPTION (adapted from the investigator's abstract): PKA and MAP kinase pathways play an important role in the control of meiotic development. Prior to the two meiotic divisions homologous chromosomes pair and undergo a very high rate of recombination, most of which are clustered near recombinational hotspots. The ade6-M26 hotspot of fission yeast is well characterized and requires a seven base pair DNA site (M26). Dr. Wahls and colleagues purified a heterodimeric protein, Mts1-Mts2-M26 complex serves as an enhancer of recombination. Mts1-Mts2 is a transcription factor of the CREB/ATF family and is phosphorylated by the MAP kinase Spc1. This may link the PKA and MAP kinase pathways in meiotic induction because Mts1-Mts2 is required for proper transcriptional regulation of cgs1+ and cgs2+. cgs1+ and cgs2+ harbor M26 sites in their 5' UTR and encode the regulatory subunit of PKA and cAMP phosphodiesterase, respectively. In contrast to the role in regulating the transcription of cgs1+ and cgs2+, Mts1-Mts2 do not significantly affect transcription at ade6-M26. The central hypothesis that forms the basis of this proposal is that Mts1-Mts2 are anti-repressors that provide DNA access for other proteins such as transcriptional activators and meiotic recombination enzymes through chromatin remodeling. The regulation of this process by MAP kinase and PKA pathways is also addressed. There are four specific aims: 1) to test the hypothesis that Mts1-Mts2 links the MAP kinase and PKA pathways to help induce meiotic development. 2) To these the hypothesis that transcriptional regulation and hotspot activation by Mts1-Mts2 are mechanistically related. 3) To test the hypothesis that Mts1-Mts2 recruits histone acetyltransferase activity to remodel chromatin structure and facilitate the assembly of the basal recombination machinery. 4) To test alternative hypotheses that the Mts1-Mts2-M26 complex either enhances the use of a pre-existing recombinational initiation site or creates a new initiation site. The PI request four years of support to carry out this study.

描述（改编自研究者的摘要）：PKA 和 MAP 激酶 途径在减数分裂发育的控制中发挥重要作用。之前 两个减数分裂同源染色体配对并经历非常高的 重组率，其中大部分聚集在重组附近 热点。裂殖酵母的 ade6-M26 热点已得到很好的表征， 需要七个碱基对 DNA 位点 (M26)。 Wahls 博士及其同事纯化了 异二聚体蛋白，Mts1-Mts2-M26 复合物作为增强子 重组。 Mts1-Mts2 是 CREB/ATF 家族的转录因子 被 MAP 激酶 Spc1 磷酸化。这可能将 PKA 和 MAP 激酶联系起来 减数分裂诱导中的途径，因为 Mts1-Mts2 是正确的减数分裂诱导所必需的 cgs1+ 和 cgs2+ 的转录调控。 cgs1+ 和 cgs2+ 海港 M26 站点 位于其 5' UTR 中并编码 PKA 和 cAMP 的调节亚基 分别是磷酸二酯酶。与调节作用相反 cgs1+和cgs2+、Mts1-Mts2的转录不会显着影响 在ade6-M26处转录。构成这一结论基础的中心假设 建议认为 Mts1-Mts2 是抗阻遏物，可为 DNA 提供通路 其他蛋白质，例如转录激活剂和减数分裂重组 酶通过染色质重塑。 MAP对该过程的调节 还讨论了激酶和 PKA 途径。有四个具体目标：1） 检验 Mts1-Mts2 将 MAP 激酶和 PKA 通路与 帮助诱导减数分裂发育。 2）对于这些假设 Mts1-Mts2 的转录调控和热点激活是 机械相关。 3）检验Mts1-Mts2招募的假设 组蛋白乙酰转移酶活性重塑染色质结构和 促进基础重组机制的组装。 4）测试 另一种假设是 Mts1-Mts2-M26 复合物增强了使用 预先存在的重组起始位点或创建新的起始位点 地点。 PI 请求四年的支持来开展这项研究。