Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination.
Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination.
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DOI：
10.1083/jcb.200909048
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发表时间：
2010-03-22
期刊：
影响因子：
--
通讯作者：
Cohen PE
中科院分区：
文献类型：
--
作者：
Holloway JK;Morelli MA;Borst PL;Cohen PE
在哺乳动物细胞中缺乏 BLM 解旋酶的情况下，不正确的染色体配对、突触和分离会损害减数分裂进程。布卢姆综合征 (BS) 是一种常染色体隐性遗传疾病，其特征是生长迟缓、癌症易感性和不育。 BS 突变 (Blm) 是 BS 患者中突变的基因，是五种哺乳动物 RecQ 解旋酶之一。尽管 BLM 已被证明可以通过协助修复体细胞同源重组过程中出现的 DNA 结构来促进基因组稳定性，但人们对其在减数分裂重组中的作用知之甚少，主要是因为与 Blm 缺失相关的胚胎致死性。然而，BLM 蛋白在减数分裂染色体上的定位以及来自酵母和其他生物体的证据表明 BLM 解旋酶在减数分裂重组事件中的作用，促使我们探索携带 Blm 条件突变等位基因的小鼠的减数分裂表型。在这项研究中，我们表明 BLM 缺陷不会影响进入前期 I，但会导致减数分裂进展的严重缺陷。同源染色体的不正确配对和突触以及重组中间体的加工改变，导致交叉增加就是例证。我们的数据首次分析了哺乳动物减数分裂中的 BLM 功能，并强烈主张 BLM 参与同源染色体的正确配对、突触和分离；然而，它对于重组中间体的积累是可有可无的。
Improper chromosome pairing, synapsis, and segregation impair meiotic progression in the absence of the BLM helicase in mammalian cells. Bloom’s syndrome (BS) is an autosomal recessive disorder characterized by growth retardation, cancer predisposition, and sterility. BS mutated (Blm), the gene mutated in BS patients, is one of five mammalian RecQ helicases. Although BLM has been shown to promote genome stability by assisting in the repair of DNA structures that arise during homologous recombination in somatic cells, less is known about its role in meiotic recombination primarily because of the embryonic lethality associated with Blm deletion. However, the localization of BLM protein on meiotic chromosomes together with evidence from yeast and other organisms implicates a role for BLM helicase in meiotic recombination events, prompting us to explore the meiotic phenotype of mice bearing a conditional mutant allele of Blm. In this study, we show that BLM deficiency does not affect entry into prophase I but causes severe defects in meiotic progression. This is exemplified by improper pairing and synapsis of homologous chromosomes and altered processing of recombination intermediates, resulting in increased chiasmata. Our data provide the first analysis of BLM function in mammalian meiosis and strongly argue that BLM is involved in proper pairing, synapsis, and segregation of homologous chromosomes; however, it is dispensable for the accumulation of recombination intermediates.
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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：
16
作者：
Jessop, Lea;Lichten, Michael
通讯作者：
Lichten, Michael
影响因子：
64.5
作者：
Boddy, MN;Gaillard, PHL;Russell, P
通讯作者：
Russell, P
DOI：
10.1073/pnas.0406157101
发表时间：
2004-11-02
影响因子：
11.1
作者：
McVey, M;LaRocque, JR;Sekelsky, JJ
通讯作者：
Sekelsky, JJ
影响因子：
3.2
作者：
KAULI, R;PRAGERLEWIN, R;LARON, Z
通讯作者：
LARON, Z