REGULATION OF MEIOTIC DEVELOPMENT BY MTS1-MTS2 PROTEIN

描述(改编自研究人员摘要)：PKA和MAP激酶 途径在减数分裂发育的控制中起着重要作用。在.之前 这两个减数分裂的同源染色体配对并经历了非常高的 重组速度，其中大部分聚集在重组附近 热点。裂解酵母的ADE6-M26热点得到了很好的表征和 需要一个七个碱基对的DNA位点(M26)。瓦尔斯博士和他的同事提纯了一种 异二聚体蛋白Mts1-MTS2-M26复合体作为一种增强剂 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激酶联系在一起 减数分裂诱导中的途径，因为Mts1-MTS2是正常的 Cgs1和cgs2的转录调控。CGS1和CGS2海港M26号场地 并编码PKA和cAMP的调节亚基 磷酸二酯酶。与其在监管 Cgs1和cgs2、mts1-mts2的转录没有显著影响 转录时间为AD6-M26。构成这一观点基础的中心假设 Mts1-MTS2是一种提供DNA通道的抗抑制因子 其他蛋白质，如转录激活因子和减数分裂重组 酶通过染色质重塑。MAP对这一过程的调控 此外，还讨论了蛋白激酶和蛋白激酶A途径。具体目标有四个：1) 验证Mts1-MTS2将MAPK和PKA通路连接到 帮助诱导减数分裂发育。2)对这些人来说，假设 Mts1-MTS2的转录调控和热点激活 从力学上讲是相关的。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 便于组装基座复合机械。4)测试 另一种假设是，Mts1-MTS2-M26复合体要么增强了用途 或创建一个新的启动 地点。国际和平研究所请求为开展这项研究提供四年的支持。

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.