Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.
Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.
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DOI：
10.1016/j.cub.2016.10.055
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发表时间：
2017-01-09
期刊：
影响因子：
--
通讯作者：
Sekelsky J
中科院分区：
文献类型：
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作者：
Hatkevich T;Kohl KP;McMahan S;Hartmann MA;Williams AM;Sekelsky J
在大多数有性生殖生物中，同源染色体之间的交叉形成是减数分裂I中染色体正确分离所必需的。在减数分裂重组过程中，程序性DNA双链断裂(DSB)的一部分被修复为交叉，其余的成为非交叉。修复中间体是否被指定为交叉是一个高度受监管的决定，它集成了几个交叉构图过程，既沿着染色体臂(干扰和着丝粒效应)，也在染色体之间(交叉保证)。由于一个多世纪以来，产生交叉模式的机制一直难以捉摸，因此很难评估交叉模式与减数分裂行为之间的关系。我们在这里表明，在缺乏布卢姆综合征解旋酶的黑腹果蝇突变体中，减数分裂交叉模式丢失。在没有干扰和着丝粒效应的情况下，交叉更均匀地分布在染色体上。交叉甚至发生在小的4号染色体上，它通常不会有减数分裂交叉。染色体对之间的交叉分布也失去了调节，导致不接受交叉的同源基因的频率增加，这反过来又导致不分离的增加。Hatkevich等人。证明果蝇布卢姆综合征解旋酶伴侣双链断裂中间产物进入减数分裂重组途径。在BLM突变体中，交叉/非交叉决定是不受调控的，导致交叉图案的丢失和非分离的增加。
In most sexually reproducing organisms, crossover formation between homologous chromosomes is necessary for proper chromosome disjunction during meiosis I. During meiotic recombination, a subset of programmed DNA double-strand breaks (DSBs) are repaired as crossovers, with the remainder becoming noncrossovers. Whether a repair intermediate is designated to become a crossover is a highly-regulated decision that integrates several crossover patterning processes, both along chromosome arms (interference and the centromere effect) and between chromosomes (crossover assurance). Because the mechanisms that generate crossover patterning have remained elusive for over a century, it has been difficult to assess the relationship between crossover patterning and meiotic chromosome behavior. We show here that meiotic crossover patterning is lost in Drosophila melanogaster mutants that lack the Bloom syndrome helicase. In the absence of interference and the centromere effect, crossovers are distributed more uniformly along chromosomes. Crossovers even occur on the small chromosome 4, which normally never has meiotic crossovers. Regulated distribution of crossovers between chromosome pairs is also lost, resulting in an elevated frequency of homologs that do not receive a crossover, which in turn leads to elevated nondisjunction. Hatkevich et al. demonstrate that the Drosophila Bloom syndrome helicase chaperones double-strand break intermediates into the meiotic recombination pathway. In Blm mutants, the crossover/noncrossover decision is unregulated, leading to loss of crossover patterning and increased nondisjunction.