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: 6227514
• 负责人: Wayne P Wahls
• 金额: $ 26.06万
• 依托单位: VANDERBILT UNIVERSITY
• 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/6227514
• 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（改编自研究者摘要）：PKA和MAP激酶 这些途径在控制减数分裂发育中起重要作用。之前 两个减数分裂同源染色体配对， 重组率，其中大部分聚集在重组附近 热点裂殖酵母的ade 6-M26热点被很好地表征， 需要一个七个碱基对的DNA位点（M26）。Wahls博士和同事纯化了一种 异二聚体蛋白，Mts 1-Mts 2-M26复合物作为增强剂， 重组Mts 1-Mts 2是CREB/ATF家族的转录因子， 被MAP激酶Spc 1磷酸化。这可能将PKA和MAP激酶 因为Mts 1-Mts 2是减数分裂诱导所必需的， cgs 1+和cgs 2+的转录调控。cgs 1+和cgs 2+携带M26位点 编码PKA和cAMP的调节亚基 磷酸二酯酶。与监管的作用相比， cgs 1+和cgs 2+的转录，Mts 1-Mts 2不显著影响cgs 1+和cgs 2+的转录， 转录于ade 6-M26。构成这一理论基础的核心假设 Mts 1-Mts 2是提供DNA通路的抗阻遏物， 其它蛋白质如转录激活因子和减数分裂重组 通过染色质重塑。MAP对这一过程的调节 激酶和PKA途径也得到解决。具体目标有四个：（1） 检验Mts 1-Mts 2将MAP激酶和PKA通路连接到 有助于诱导减数分裂发育。2)对于这些假设， Mts 1-Mts 2的转录调控和热点激活是 机械相关。3)为了验证Mts 1-Mts 2招募 组蛋白乙酰转移酶活性以重塑染色质结构， 便于基础重组机构的组装。4)测试 Mts 1-Mts 2-M26复合体或增强使用的替代假设 或产生新的起始位点 绝佳的价钱主要研究者要求提供四年的支持来开展这项研究。