Hollingsworth Nancy M
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215.
Microb Cell. 2016 Feb 22;3(3):129-131. doi: 10.15698/mic2016.03.487.
Sexually reproducing organisms create gametes with half the somatic cell chromosome number so that fusion of gametes at fertilization does not change the ploidy of the cell. This reduction in chromosome number occurs by the specialized cell division of meiosis in which two rounds of chromosome segregation follow a single round of chromosome duplication. Meiotic crossovers formed between the non-sister chromatids of homologous chromosomes, combined with sister chromatid cohesion, physically connect homologs, thereby allowing proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs) whose repair is highly regulated such that (1) there is a bias for recombination with homologs rather than sister chromatids, (2) crossovers are distributed throughout the genome by a process called interference, (3) crossover homeostasis regulates the balance between crossover and non-crossover repair to maintain a critical number of crossovers and (4) each pair of homologs receives at least one crossover. It was previously known that the imposition of interhomolog bias in budding yeast requires meiosis-specific modifications to the DNA damage response and the local activation of the meiosis-specific Mek1/Mre4 (hereafter Mek1) kinase at DSBs. However, because inactivation of Mek1 results in intersister, rather than interhomolog DSB repair, whether Mek1 had a role in interhomolog pathway choice was unknown. A recent study by Chen . (2015) reveals that Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference. It does this by enabling phosphorylation of Zip1, the meiosis-specific transverse filament protein of the synaptonemal complex (SC), by the conserved cell cycle kinase, Cdc7-Dbf4 (DDK). These results suggest that Mek1 is a "master regulator" of meiotic recombination in budding yeast.
有性生殖的生物体产生的配子所含染色体数目是体细胞染色体数目的一半，这样在受精时配子融合就不会改变细胞的倍性。染色体数目的这种减少是通过减数分裂这种特殊的细胞分裂实现的，在减数分裂过程中，一轮染色体复制之后会有两轮染色体分离。同源染色体的非姐妹染色单体之间形成的减数分裂交叉，与姐妹染色单体黏连相结合，在物理上连接了同源染色体，从而使得在第一次减数分裂时能够正确分离。减数分裂重组由程序性双链断裂（DSB）引发，其修复受到高度调控，使得：（1）与同源染色体而非姐妹染色单体发生重组存在偏向性；（2）交叉通过一种称为干涉的过程分布于整个基因组；（3）交叉稳态调节交叉修复与非交叉修复之间的平衡，以维持关键数量的交叉；（4）每对同源染色体至少接受一次交叉。此前已知，在芽殖酵母中施加同源染色体偏向性需要对DNA损伤反应进行减数分裂特异性修饰，以及在DSB处局部激活减数分裂特异性的Mek1/Mre4（以下简称Mek1）激酶。然而，由于Mek1失活会导致姐妹染色单体之间而非同源染色体之间的DSB修复，所以Mek1在同源染色体途径选择中是否起作用尚不清楚。Chen等人（2015年）最近的一项研究表明，Mek1间接调节同源染色体之间的交叉/非交叉决定以及遗传干涉。它通过使保守的细胞周期激酶Cdc7-Dbf4（DDK）能够磷酸化Zip1来实现这一点，Zip1是联会复合体（SC）的减数分裂特异性横向细丝蛋白。这些结果表明，Mek1是芽殖酵母减数分裂重组的“主调控因子”。
