Davis L, Barbera M, McDonnell A, McIntyre K, Sternglanz R, Jin Q, Loidl J, Engebrecht J
Department of Pharmacological Sciences, Graduate Program in Genetics, State University of New York, Stony Brook, New York 11794-8651, USA.
Genetics. 2001 Mar;157(3):1179-89. doi: 10.1093/genetics/157.3.1179.
The Saccharomyces cerevisiae MUM2 gene is essential for meiotic, but not mitotic, DNA replication and thus sporulation. Genetic interactions between MUM2 and a component of the origin recognition complex and polymerase alpha-primase suggest that MUM2 influences the function of the DNA replication machinery. Early meiotic gene expression is induced to a much greater extent in mum2 cells than in meiotic cells treated with the DNA synthesis inhibitor hydroxyurea. This result indicates that the mum2 meiotic arrest is downstream of the arrest induced by hydroxyurea and suggests that DNA synthesis is initiated in the mutant. Genetic analyses indicate that the recombination that occurs in mum2 mutants is dependent on the normal recombination machinery and on synaptonemal complex components and therefore is not a consequence of lesions created by incompletely replicated DNA. Both meiotic ectopic and allelic recombination are similarly reduced in the mum2 mutant, and the levels are consistent with the levels of meiosis-specific DSBs that are generated. Cytological analyses of mum2 mutants show that chromosome pairing and synapsis occur, although at reduced levels compared to wild type. Given the near-wild-type levels of meiotic gene expression, pairing, and synapsis, we suggest that the reduction in DNA replication is directly responsible for the reduced level of DSBs and meiotic recombination.
酿酒酵母MUM2基因对于减数分裂而非有丝分裂的DNA复制以及因此对于孢子形成至关重要。MUM2与起始识别复合物的一个组分以及聚合酶α-引发酶之间的遗传相互作用表明，MUM2影响DNA复制机器的功能。与用DNA合成抑制剂羟基脲处理的减数分裂细胞相比，mum2细胞中早期减数分裂基因表达的诱导程度要大得多。这一结果表明，mum2减数分裂阻滞位于羟基脲诱导的阻滞的下游，并提示在该突变体中DNA合成已启动。遗传分析表明，mum2突变体中发生的重组依赖于正常的重组机制和联会复合体组分，因此不是由未完全复制的DNA产生的损伤所导致的结果。在mum2突变体中，减数分裂异位重组和等位基因重组均同样减少，且其水平与所产生的减数分裂特异性双链断裂的水平一致。对mum2突变体的细胞学分析表明，染色体配对和联会会发生，尽管与野生型相比水平有所降低。鉴于减数分裂基因表达、配对和联会接近野生型水平，我们认为DNA复制的减少直接导致了双链断裂水平和减数分裂重组水平的降低。
