Long telomeres are preferentially extended during recombination-mediated telomere maintenance.

Long telomeres are preferentially extended during recombination-mediated telomere maintenance.
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DOI:
10.1038/nsmb.2034
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发表时间:
2011-04
影响因子:
16.8
通讯作者:
--
中科院分区:
生物学1区
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--
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大多数人体细胞不表达端粒酶。因此,随着每次细胞分裂,它们的端粒逐渐缩短,直到诱导复制衰老。大约15%的人类癌症使用端粒不依赖的、基于重组的机制来维持其端粒,这些机制统称为端粒替代性延长(ALT)。在酿酒酵母中,ALT细胞被称为“幸存者”。一种类型的幸存者(II型)类似于人类ALT细胞,因为两者都是通过端粒重复序列的扩增来定义的。我们分析了重组介导的端粒延伸事件在个别端粒端粒酶阴性酵母在II型幸存者形成过程中,发现长端粒优先延长。此外,我们发现具有长端粒的衰老细胞更有效地通过II型途径绕过衰老。我们推测,端粒长度可能是重要的,在确定是否癌细胞利用端粒酶或ALT绕过复制衰老。
Most human somatic cells do not express telomerase. Consequently, with each cell division their telomeres progressively shorten until replicative senescence is induced. Approximately 15% of human cancers maintain their telomeres using telomerase-independent, recombination-based mechanisms collectively termed Alternative Lengthening of Telomeres (ALT). In the yeast Saccharomyces cerevisiae, ALT cells are referred to as “survivors”. One type of survivor (type II) resembles human ALT cells in that both are defined by the amplification of telomeric repeats. We analyzed recombination-mediated telomere extension events at individual telomeres in telomerase-negative yeast during type II survivor formation and find that long telomeres are preferentially extended. Furthermore, we find that senescent cells with long telomeres are more efficient at bypassing senescence via the type II pathway. We speculate that telomere length may be important in determining whether cancer cells utilize telomerase or ALT to bypass replicative senescence.
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