Telomere dysfunction increases mutation rate and genomic instability
Telomere dysfunction increases mutation rate and genomic instability
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DOI：
10.1016/s0092-8674(01)00457-3
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发表时间：
2001-08-10
期刊：
影响因子：
64.5
通讯作者：
Greider, CW
中科院分区：
文献类型：
--
作者：
Hackett, JA;Feldser, DM;Greider, CW
端粒酶缺失小鼠中肿瘤发病率的增加表明端粒功能障碍诱导遗传不稳定性。为了直接验证这一点，我们检测了S.啤酒。随着端粒功能失调，在est 1 Delta菌株中CAN 1基因的突变率增加了10到100倍。这种增加的突变率是由于末端缺失频率增加所致。从est 1 Delta菌株中回收染色体融合，表明末端缺失可能通过断裂-融合-桥型机制发生。在一个位点，染色体末端缺失获得了一个新的端粒通过Rad 52 p依赖，Rad 51 p独立的过程与断裂诱导复制一致。在第二个基因座，更复杂的重排涉及多个染色体被视为。这些数据表明，端粒酶可以抑制染色体不稳定性。
The increased tumor incidence in telomerase null mice suggests that telomere dysfunction induces genetic instability. To test this directly, we examined mutation rate in the absence of telomerase in S. cerevisiae. The mutation rate in the CAN1 gene increased 10- to 100-fold in est1 Delta strains as telomeres became dysfunctional. This increased mutation rate resulted from an increased frequency of terminal deletions. Chromosome fusions were recovered from est1 Delta strains, suggesting that the terminal deletions may occur by a breakage-fusion-bridge type mechanism. At one locus, chromosomes with terminal deletions gained a new telomere through a Rad52p-dependent, Rad51p-independent process consistent with break-induced replication. At a second locus, more complicated rearrangements involving multiple chromosomes were seen. These data suggest that telomerase can inhibit chromosomal instability.