Murakami H, Nurse P
Cell Cycle Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK.
Genes Dev. 1999 Oct 1;13(19):2581-93. doi: 10.1101/gad.13.19.2581.
In eukaryotes, the DNA replication checkpoint prevents entry into mitosis when DNA replication is incomplete and is crucial for maintaining genomic integrity. Much less is known about equivalent controls that operate during meiosis. Here, we show that a DNA replication checkpoint control operates during meiosis in fission yeast. The mitotic checkpoint Rad genes and the Cds1 protein kinase are required for the DNA replication checkpoint during meiosis, with Cds1 playing a more prominent role than it does during mitosis. When DNA replication is blocked, the checkpoint maintains Cdc2 tyrosine 15 phosphorylation keeping Cdc2 protein kinase activity low and preventing onset of meiosis I. Additionally, there is a second checkpoint acting during meiosis that is revealed if cells are prevented from maintaining Cdc2 tyrosine 15 phosphorylation when DNA replication is blocked. Such cells arrest with high Cdc2 protein kinase activity and separated spindle pole bodies, an arrest state similar to that observed in mitotic budding yeast cells when DNA replication is incomplete. This second checkpoint is meiosis specific and may reflect processes occurring only during meiosis such as increased recombination rates, an extended duration of nuclear division, or homolog chromosome pairing.
在真核生物中,DNA复制检查点可防止在DNA复制不完全时进入有丝分裂,对于维持基因组完整性至关重要。关于在减数分裂过程中起作用的等效控制机制,人们了解得要少得多。在这里,我们表明,DNA复制检查点控制在裂殖酵母的减数分裂过程中起作用。有丝分裂检查点Rad基因和Cds1蛋白激酶在减数分裂期间的DNA复制检查点中是必需的,其中Cds1发挥的作用比在有丝分裂期间更为突出。当DNA复制受阻时,检查点维持Cdc2酪氨酸15位点的磷酸化,使Cdc2蛋白激酶活性保持在低水平,并阻止减数分裂I的开始。此外,在减数分裂过程中还有第二个检查点,如果在DNA复制受阻时阻止细胞维持Cdc2酪氨酸15位点的磷酸化,这个检查点就会显现出来。这些细胞会因Cdc2蛋白激酶活性高和纺锤极体分离而停滞,这种停滞状态类似于在有丝分裂的芽殖酵母细胞中DNA复制不完全时观察到的情况。这个第二个检查点是减数分裂特有的,可能反映了仅在减数分裂过程中发生的过程,如重组率增加、核分裂持续时间延长或同源染色体配对。