San-Segundo P A, Roeder G S
Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
Mol Biol Cell. 2000 Oct;11(10):3601-15. doi: 10.1091/mbc.11.10.3601.
During the meiotic cell cycle, a surveillance mechanism called the "pachytene checkpoint" ensures proper chromosome segregation by preventing meiotic progression when recombination and chromosome synapsis are defective. The silencing protein Dot1 (also known as Pch1) is required for checkpoint-mediated pachytene arrest of the zip1 and dmc1 mutants of Saccharomyces cerevisiae. In the absence of DOT1, the zip1 and dmc1 mutants inappropriately progress through meiosis, generating inviable meiotic products. Other components of the pachytene checkpoint include the nucleolar protein Pch2 and the heterochromatin component Sir2. In dot1, disruption of the checkpoint correlates with the loss of concentration of Pch2 and Sir2 in the nucleolus. In addition to its checkpoint function, Dot1 blocks the repair of meiotic double-strand breaks by a Rad54-dependent pathway of recombination between sister chromatids. In vegetative cells, mutation of DOT1 results in delocalization of Sir3 from telomeres, accounting for the impaired telomeric silencing in dot1.
在减数分裂细胞周期中，一种名为“粗线期检查点”的监测机制通过在重组和染色体联会有缺陷时阻止减数分裂进程，确保染色体正确分离。沉默蛋白Dot1（也称为Pch1）是酿酒酵母zip1和dmc1突变体检查点介导的粗线期停滞所必需的。在没有DOT1的情况下，zip1和dmc1突变体在减数分裂过程中不恰当地进行，产生不可存活的减数分裂产物。粗线期检查点的其他成分包括核仁蛋白Pch2和异染色质成分Sir2。在dot1中，检查点的破坏与核仁中Pch2和Sir2浓度的丧失相关。除了其检查点功能外，Dot1还通过姐妹染色单体之间依赖Rad54的重组途径阻断减数分裂双链断裂的修复。在营养细胞中，DOT1的突变导致Sir3从端粒上脱离，这解释了dot1中端粒沉默受损的原因。
