Meiotic recombination initiation in and around retrotransposable elements in Saccharomyces cerevisiae.
Meiotic recombination initiation in and around retrotransposable elements in Saccharomyces cerevisiae.
复制标题
在酿酒酵母中及其周围的逆转元素内及其周围的减数分裂重组。
DOI：
10.1371/journal.pgen.1003732
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发表时间：
2013-08
期刊：
影响因子：
4.5
通讯作者：
Keeney S
中科院分区：
文献类型：
--
作者：
Sasaki M;Tischfield SE;van Overbeek M;Keeney S
减数分裂重组是由大量发育程序性DNA双链断裂（DSB）启动的，根据生物体的不同，每个细胞的DSB数量从几十到几百不等。在单拷贝序列中形成的DSB引起同源染色体上等位基因位置之间的重组，但DSB也可以在重复元件如反转录转座子中或附近形成。当它们这样做时，它们通过非等位重复序列之间的重组在生殖系中产生有害基因组重排的风险。先前在芽殖酵母中的研究表明，将Ty反转录转座子插入DSB热点中可以抑制减数分裂断裂形成，但是Ty元件在其最常见的生理环境中的性质尚未得到解决。在这里，我们编制了一个全面的，高分辨率的地图，所有的泰元素在快速和有效地孢子S。酿酒酵母菌株SK 1，并检查这些内源性逆转录转座因子中和附近的DSB形成。SK 1有30个Tys，除了一个Tys之外，其余都与酵母参考基因组的源菌株S288 C中的50个Tys不同。从全基因组DSB图谱和直接分子检测，我们发现，DSB水平和染色质结构内和附近的Tys不同的元素之间的差异很大，并认为当地DSB抑制是不是一个普遍的功能Ty的存在。令人惊讶的是，两个Ty元件的缺失削弱了邻近的DSB热点，这表明至少一些Ty插入促进而不是抑制附近的DSB形成。鉴于高应变Ty的位置和高聚合负担的Ty-proximal DSB的应变变异，我们建议，减数分裂重组是一个重要组成部分的主机Ty的相互作用和Tys在基因组的不稳定性和进化中发挥关键作用，在近交和异交性周期。减数分裂是产生配子进行有性生殖的细胞分裂。在减数分裂期间，同源重组频繁发生，由Spo 11产生的DNA双链断裂（DSB）启动。减数分裂重组通常发生在同源染色体上等位基因位置的序列之间，但是重复元件内的DSB（例如，反转录转座子）可以引起非等位基因序列之间的重组。这可能会造成严重的染色体重排形式的基因组破坏，这是许多复发性人类突变的基础。人们认为，细胞通过不利于重复元件中的DSB形成来最大限度地降低这种风险，部分基于研究表明Ty元件（酵母逆转录转座子）的存在可以抑制附近的DSB活性。然而，这是否是Tys的一般特征尚未评估。在这里，我们产生了一个全面的地图Tys在迅速形成孢子的SK 1菌株，并检查DSB的形成和周围的所有这些内源性Ty元素。值得注意的是，大多数天然Ty元素似乎并不抑制附近DSB的形成，至少其中一些增加了局部DSB。这些发现对于理解宿主和转座子之间的关系，以及理解逆转录转座子对有性生殖过程中基因组稳定性和进化的影响具有重要意义。
Meiotic recombination is initiated by large numbers of developmentally programmed DNA double-strand breaks (DSBs), ranging from dozens to hundreds per cell depending on the organism. DSBs formed in single-copy sequences provoke recombination between allelic positions on homologous chromosomes, but DSBs can also form in and near repetitive elements such as retrotransposons. When they do, they create a risk for deleterious genome rearrangements in the germ line via recombination between non-allelic repeats. A prior study in budding yeast demonstrated that insertion of a Ty retrotransposon into a DSB hotspot can suppress meiotic break formation, but properties of Ty elements in their most common physiological contexts have not been addressed. Here we compile a comprehensive, high resolution map of all Ty elements in the rapidly and efficiently sporulating S. cerevisiae strain SK1 and examine DSB formation in and near these endogenous retrotransposable elements. SK1 has 30 Tys, all but one distinct from the 50 Tys in S288C, the source strain for the yeast reference genome. From whole-genome DSB maps and direct molecular assays, we find that DSB levels and chromatin structure within and near Tys vary widely between different elements and that local DSB suppression is not a universal feature of Ty presence. Surprisingly, deletion of two Ty elements weakened adjacent DSB hotspots, revealing that at least some Ty insertions promote rather than suppress nearby DSB formation. Given high strain-to-strain variability in Ty location and the high aggregate burden of Ty-proximal DSBs, we propose that meiotic recombination is an important component of host-Ty interactions and that Tys play critical roles in genome instability and evolution in both inbred and outcrossed sexual cycles. Meiosis is the cell division that generates gametes for sexual reproduction. During meiosis, homologous recombination occurs frequently, initiated by DNA double-strand breaks (DSBs) made by Spo11. Meiotic recombination usually occurs between sequences at allelic positions on homologous chromosomes, but a DSB within a repetitive element (e.g., a retrotransposon) can provoke recombination between non-allelic sequences instead. This can create genomic havoc in the form of gross chromosomal rearrangements, which underlie many recurrent human mutations. It has been thought that cells minimize this risk by disfavoring DSB formation in repetitive elements, partly based on studies showing that presence of a Ty element (a yeast retrotransposon) can suppress nearby DSB activity. Whether this is a general feature of Tys has not been evaluated, however. Here, we generated a comprehensive map of Tys in the rapidly sporulating SK1 strain and examined DSB formation in and around all of these endogenous Ty elements. Remarkably, most natural Ty elements do not appear to suppress DSB formation nearby, and at least some of them increase local DSBs. These findings have implications for understanding the relationship between host and transposon, and for understanding the impact of retrotransposons on genome stability and evolution during sexual reproduction.
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映射减数分裂的单链DNA揭示了酿酒酵母中DNA双链断裂的新景观。
影响因子：
9.8
作者：
Buhler, Cyril;Borde, Valerie;Lichten, Michael
通讯作者：
Lichten, Michael
影响因子：
1.7
作者：
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通讯作者：
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DOI：
10.1073/pnas.97.17.9537
发表时间：
2000-08-15
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
10.5
作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
KLECKNER, N