Yamada Shintaro, Okamura Mika, Oda Arisa, Murakami Hiroshi, Ohta Kunihiro, Yamada Takatomi
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Japan.
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 113-0032, Japan.
Genetics. 2017 Jun;206(2):801-809. doi: 10.1534/genetics.116.197954. Epub 2017 Apr 10.
Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA double-strand breaks (DSBs) formed at recombination hotspots. Meiotic DSB formation is likely to be influenced by other DNA-templated processes including transcription, but how DSB formation and transcription interact with each other has not been understood well. In this study, we used fission yeast to investigate a possible interplay of these two events. A group of hotspots in fission yeast are associated with sequences similar to the cyclic AMP response element and activated by the ATF/CREB family transcription factor dimer Atf1-Pcr1. We first focused on one of those hotspots, , and Atf1. Our results showed that multiple transcripts, shorter than the full-length messenger RNA, emanate from a region surrounding the hotspot. Interestingly, we found that the previously known recombination-activation region of Atf1 is also a transactivation domain, whose deletion affected DSB formation and short transcript production at These results point to a possibility that the two events may be related to each other at In fact, comparison of published maps of meiotic transcripts and hotspots suggested that hotspots are very often located close to meiotically transcribed regions. These observations therefore propose that meiotic DSB formation in fission yeast may be connected to transcription of surrounding regions.
减数分裂同源重组是确保染色体忠实分离和创造遗传多样性的关键事件，它由在重组热点形成的程序性DNA双链断裂（DSB）引发。减数分裂DSB的形成可能受包括转录在内的其他DNA模板化过程的影响，但DSB形成与转录如何相互作用尚未得到很好的理解。在本研究中，我们使用裂殖酵母来研究这两个事件之间可能的相互作用。裂殖酵母中的一组热点与类似于环磷酸腺苷反应元件的序列相关，并由ATF/CREB家族转录因子二聚体Atf1-Pcr1激活。我们首先聚焦于其中一个热点以及Atf1。我们的结果表明，从围绕该热点的区域产生了多个比全长信使RNA短的转录本。有趣的是，我们发现Atf1先前已知的重组激活区域也是一个反式激活结构域，其缺失影响了该热点处的DSB形成和短转录本的产生。这些结果表明这两个事件在该热点处可能相互关联。事实上，已发表的减数分裂转录本图谱与热点图谱的比较表明，热点常常位于减数分裂转录区域附近。因此，这些观察结果表明裂殖酵母中的减数分裂DSB形成可能与周围区域的转录相关。
