Regulation of mitotic recombination between DNA repeats in centromeres.
Regulation of mitotic recombination between DNA repeats in centromeres.
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DOI：
10.1093/nar/gkx763
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发表时间：
2017-11-02
影响因子：
14.9
通讯作者：
Nakagawa T
中科院分区：
文献类型：
--
作者：
Zafar F;Okita AK;Onaka AT;Su J;Katahira Y;Nakayama JI;Takahashi TS;Masukata H;Nakagawa T
在许多真核生物中，着丝粒由独特的DNA重复序列组成，对染色体的忠实分离至关重要。虽然在减数分裂过程中着丝粒周围的重组是不充分的，很少有人知道有丝分裂细胞中的着丝粒重复之间的重组。在这里，我们比较了自发重组，发生在整合在着丝粒1（cen 1）或在非着丝粒ura 4基因座在裂殖酵母的ade 6 B/ade 6X反向重复序列。值得注意的是，在着丝粒和非着丝粒区域观察到不同的同源重组（HR）机制。Rad 51依赖的HR需要Rad 51，Rad 54和Rad 52是占主导地位的着丝粒，而Rad 51独立的HR需要Rad 52也发生在手臂区域。与臂区域相比，在着丝粒中反向重复序列（即倒位）之间的交叉代表性不足。当异染色质被抑制时，需要Mhf 1/CENP-S、Mhf 2/CENP-X组蛋白折叠蛋白和Fml 1/FANCM解旋酶来抑制交叉。此外，Mhf 1和Fml 1被发现可以防止由着丝粒重复介导的总染色体重排。这些数据揭示了着丝粒中DNA重复序列之间的有丝分裂重组的调节及其在维持基因组完整性中的生理作用。
Centromeres that are essential for faithful segregation of chromosomes consist of unique DNA repeats in many eukaryotes. Although recombination is under-represented around centromeres during meiosis, little is known about recombination between centromere repeats in mitotic cells. Here, we compared spontaneous recombination that occurs between ade6B/ade6X inverted repeats integrated at centromere 1 (cen1) or at a non-centromeric ura4 locus in fission yeast. Remarkably, distinct mechanisms of homologous recombination (HR) were observed in centromere and non-centromere regions. Rad51-dependent HR that requires Rad51, Rad54 and Rad52 was predominant in the centromere, whereas Rad51-independent HR that requires Rad52 also occurred in the arm region. Crossovers between inverted repeats (i.e. inversions) were under-represented in the centromere as compared to the arm region. While heterochromatin was dispensable, Mhf1/CENP–S, Mhf2/CENP–X histone-fold proteins and Fml1/FANCM helicase were required to suppress crossovers. Furthermore, Mhf1 and Fml1 were found to prevent gross chromosomal rearrangements mediated by centromere repeats. These data uncovered the regulation of mitotic recombination between DNA repeats in centromeres and its physiological role in maintaining genome integrity.
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影响因子：
4.5
作者：
de Koning AP;Gu W;Castoe TA;Batzer MA;Pollock DD
通讯作者：
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影响因子：
2.6
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通讯作者：
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