Dahlen M, Olsson T, Kanter-Smoler G, Ramne A, Sunnerhagen P
Department of Molecular Biology, Lundberg Laboratory, Goteborg University, S-405 30 Goteborg, Sweden.
Mol Biol Cell. 1998 Mar;9(3):611-21. doi: 10.1091/mbc.9.3.611.
We have studied telomere length in Schizosaccharomyces pombe strains carrying mutations affecting cell cycle checkpoints, DNA repair, and regulation of the Cdc2 protein kinase. Telomere shortening was found in rad1, rad3, rad17, and rad26 mutants. Telomere lengths in previously characterized rad1 mutants paralleled the replication checkpoint proficiency of those mutants. In contrast, rad9, chk1, hus1, and cds1 mutants had intact telomeres. No difference in telomere length was seen in mutants affected in the regulation of Cdc2, whereas some of the DNA repair mutants examined had slightly longer telomeres than did the wild type. Overexpression of the rad1(+) gene caused telomeres to elongate slightly. The kinetics of telomere shortening was monitored by following telomere length after disruption of the rad1(+) gene; the rate was approximately 1 nucleotide per generation. Wild-type telomere length could be restored by reintroduction of the wild-type rad1(+) gene. Expression of the Saccharomyces cerevisiae RCK1 protein kinase gene, which suppresses the radiation and hydroxyurea sensitivity of Sz. pombe checkpoint mutants, was able to attenuate telomere shortening in rad1 mutant cells and to increase telomere length in a wild-type background. The functional effects of telomere shortening in rad1 mutants were assayed by measuring loss of a linear and a circular minichromosome. A minor increase in loss rate was seen with the linear minichromosome, and an even smaller difference compared with wild-type was detected with the circular plasmid.
我们研究了粟酒裂殖酵母菌株中的端粒长度,这些菌株携带影响细胞周期检查点、DNA修复以及Cdc2蛋白激酶调控的突变。在rad1、rad3、rad17和rad26突变体中发现了端粒缩短现象。先前已表征的rad1突变体中的端粒长度与这些突变体的复制检查点能力平行。相比之下,rad9、chk1、hus1和cds1突变体的端粒是完整的。在受Cdc2调控影响的突变体中未观察到端粒长度的差异,而所检测的一些DNA修复突变体的端粒比野生型略长。rad1(+)基因的过表达导致端粒略有延长。通过跟踪rad1(+)基因破坏后端粒长度来监测端粒缩短的动力学;速率约为每代1个核苷酸。野生型端粒长度可通过重新引入野生型rad1(+)基因来恢复。酿酒酵母RCK1蛋白激酶基因的表达可抑制粟酒裂殖酵母检查点突变体对辐射和羟基脲的敏感性,该基因能够减弱rad1突变体细胞中的端粒缩短,并在野生型背景下增加端粒长度。通过测量线性和环状微型染色体的丢失来检测rad1突变体中端粒缩短的功能效应。线性微型染色体的丢失率略有增加,与野生型相比,环状质粒的差异更小。