Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion
Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion
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DOI：
10.7554/elife.21900
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发表时间：
2017-01-04
期刊：
影响因子：
7.7
通讯作者：
Borde, Valerie
中科院分区：
文献类型：
--
作者：
Duroc, Yann;Kumar, Rajeev;Borde, Valerie
减数分裂重组引起的基因转换对形成基因组多样化和进化至关重要。目前尚不清楚基因转化的程度是如何受到调控的。在这里，我们证明了萌芽酵母错配修复相关的MutLβ复合体MLH1-Mlh2特定地与保守的减数分裂Mer3解旋酶相互作用，该酶独立于错配识别而招募到重组热点。在不影响交叉形成的情况下，这种招募对于限制全基因组范围内的基因转换道长度是必不可少的。与预期相反，Mer3解旋酶活性，被认为延长了置换环(D-loop)重组中间产物，并不影响基因转换事件的长度，揭示了Mer3的非催化作用。此外，纯化的Mer3和MutLβ都优先识别D-环，为限制体内的基因转换提供了一种机制。这些发现表明，MutLβ是减数分裂重组新调控步骤的一个组成部分，这对防止种群中的快速等位基因固定和热点侵蚀具有重要意义。
Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutL beta complex, Mlh1-Mlh2, specifically inter acts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting cross over formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutL beta preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutL beta is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.