Age-Dependent Alterations in Meiotic Recombination Cause Chromosome Segregation Errors in Spermatocytes.
Age-Dependent Alterations in Meiotic Recombination Cause Chromosome Segregation Errors in Spermatocytes.
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DOI：
10.1016/j.cell.2017.08.042
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发表时间：
2017-10-19
期刊：
影响因子：
64.5
通讯作者：
Cole F
中科院分区：
文献类型：
--
作者：
Zelazowski MJ;Sandoval M;Paniker L;Hamilton HM;Han J;Gribbell MA;Kang R;Cole F
在减数分裂中的忠实染色体分离需要交叉（CO）重组，其被调节以确保每个同源物对至少一个CO。我们调查未能确保在少年雄性小鼠的CO。通过监测重组全基因组使用细胞学检测和热点使用分子检测，我们表明，青少年小鼠精母细胞有较少的CO相对于成年人。在MLH 3的情况下重组的分析提供了证据，更大的利用青少年的途径，涉及结构选择性核酸酶和/或替代复合物，它可以作用于前体产生noncrossovers（NCO）的代价CO。我们建议，一些指定的CO网站未能在青少年有效地成熟，由于这些替代修复途径的不适当的活动，导致染色体错误分离。我们还发现，在青少年人类精母细胞中MutLγ灶密度较低，这表明较弱的CO成熟效率可能解释了为什么年轻男性有较高的唐氏综合征患儿风险。年轻男性中有效减数分裂交叉重组的发生率较低，这归因于优先利用涉及结构选择性核酸内切酶和/或以交叉为代价产生非交叉的替代复合物的途径。
Faithful chromosome segregation in meiosis requires crossover (CO) recombination, which is regulated to ensure at least one CO per homolog pair. We investigate failure to ensure COs in juvenile male mice. By monitoring recombination genome-wide using cytological assays and at hotspots using molecular assays, we show that juvenile mouse spermatocytes have fewer COs relative to adults. Analysis of recombination in the absence of MLH3 provides evidence for greater utilization in juveniles of pathways involving structure-selective nucleases and/or alternative complexes, which can act upon precursors to generate noncrossovers (NCOs) at the expense of COs. We propose that some designated CO sites fail to mature efficiently in juveniles owing to inappropriate activity of these alternative repair pathways, leading to chromosome mis-segregation. We also find lower MutLγ focus density in juvenile human spermatocytes, suggesting that weaker CO maturation efficiency may explain why younger men have higher risk of fathering children with Down syndrome. A lower incidence of efficient meiotic crossover recombination in young males attributed to the preferred utilization of pathways involving structure-selective endonucleases and/or alternative complexes that generate non-crossovers at the expense of crossovers.
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影响因子：
4.5
作者：
Holloway JK;Booth J;Edelmann W;McGowan CH;Cohen PE
通讯作者：
Cohen PE
影响因子：
56.9
作者：
Lynn, A;Koehler, KE;Hassold, TJ
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Hassold, TJ
DOI：
10.1126/science.1219379
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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Bishop DK
影响因子：
5.3
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：
Goldman, ASH;Lichten, M
通讯作者：
Lichten, M