REC, Drosophila MCM8, drives formation of meiotic crossovers
REC, Drosophila MCM8, drives formation of meiotic crossovers
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果蝇 MCM8 REC 驱动减数分裂交叉的形成
DOI：
10.1371/journal.pgen.0010040
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发表时间：
2005-09-01
期刊：
影响因子：
4.5
通讯作者：
Sekelsky, J
中科院分区：
文献类型：
--
作者：
Blanton, HL;Radford, SJ;Sekelsky, J
在减数分裂过程中，杂交确保同源染色体彼此之间的精确分离。在这里，我们描述的身份和功能的果蝇基因重组缺陷（rec），这是需要大多数减数分裂的交叉。我们发现，rec编码的迷你染色体维护（MCM）蛋白家族的成员。六种MCM蛋白（MCM 2 -7）是DNA复制所必需的，存在于所有真核生物中。REC是最近发现的该家族第七个成员MCM 8的果蝇直系同源物。我们的系统发育分析揭示了另一个家族成员MCM 9的存在，并表明MCM 8和MCM 9在真核生物进化的早期出现，尽管其中一个或两个在多个真核生物谱系中丢失。果蝇已失去了MCM 9，但保留了MCM 8，以REC为代表。我们用遗传学和分子生物学方法研究REC在减数分裂重组中的功能。上位性实验表明REC在Rad 51直系同源物SPN-A之后但在内切核酸酶MEI-9之前起作用。虽然在rec突变体中，交换减少了95%，但非交换基因转换的频率显著增加。有趣的是，rec突变体中的基因转换束大约是野生型果蝇中基因转换束长度的一半。为了解释这些表型，我们建议REC促进减数分裂重组过程中的修复合成。在不存在REC的情况下，合成进行得不足以形成可引起交叉的中间体，并且重组通过合成依赖性链退火进行以仅产生非交叉产物。
Crossovers ensure the accurate segregation of homologous chromosomes from one another during meiosis. Here, we describe the identity and function of the Drosophila melanogaster gene recombination defective (rec), which is required for most meiotic crossing over. We show that rec encodes a member of the mini-chromosome maintenance (MCM) protein family. Six MCM proteins (MCM2-7) are essential for DNA replication and are found in all eukaryotes. REC is the Drosophila ortholog of the recently identified seventh member of this family, MCM8. Our phylogenetic analysis reveals the existence of yet another family member, MCM9, and shows that MCM8 and MCM9 arose early in eukaryotic evolution, though one or both have been lost in multiple eukaryotic lineages. Drosophila has lost MCM9 but retained MCM8, represented by REC. We used genetic and molecular methods to study the function of REC in meiotic recombination. Epistasis experiments suggest that REC acts after the Rad51 ortholog SPN-A but before the endonuclease MEI-9. Although crossovers are reduced by 95% in rec mutants, the frequency of noncrossover gene conversion is significantly increased. Interestingly, gene conversion tracts in rec mutants are about half the length of tracts in wild-type flies. To account for these phenotypes, we propose that REC facilitates repair synthesis during meiotic recombination. In the absence of REC, synthesis does not proceed far enough to allow formation of an intermediate that can give rise to crossovers, and recombination proceeds via synthesis-dependent strand annealing to generate only noncrossover products.