Role of mammalian Rad54 in telomere length maintenance
Role of mammalian Rad54 in telomere length maintenance
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DOI：
10.1128/mcb.23.16.5572-5580.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Jaco, I;Mu単oz, P;Blasco, MA
同源重组（HR） DNA修复途径参与酵母端粒长度维持，但其在哺乳动物端粒中的推测作用尚不清楚。哺乳动物Rad54是HR机制的一部分，Rad54缺陷小鼠的HR能力下降。在这里，我们发现Rad54缺陷小鼠的端粒也比野生型对照显着缩短，这表明Rad54活性在哺乳动物端粒长度维持中起着至关重要的作用。与对照组相比，Rad54缺失还导致端粒端到端染色体融合频率增加，这表明Rad54可能在端粒盖帽中起作用。最后，对Rad54和DNA-PKcs双缺陷小鼠的研究表明，在缺乏Rad54的情况下，由于DNA-PKcs缺陷引起的端粒融合不会被挽救，这表明它们不受Rad54活性的介导。
The homologous recombination (HR) DNA repair pathway participates in telomere length maintenance in yeast but its putative role at mammalian telomeres is unknown. Mammalian Rad54 is part of the HR machinery, and Rad54-deficient mice show a reduced HR capability. Here, we show that Rad54-deficient mice also show significantly shorter telomeres than wild-type controls, indicating that Rad54 activity plays an essential role in telomere length maintenance in mammals. Rad54 deficiency also resulted in an increased frequency of end-to-end chromosome fusions involving telomeres compared to the controls, suggesting a putative role of Rad54 in telomere capping. Finally, the study of mice doubly deficient for Rad54 and DNA-PKcs showed that telomere fusions due to DNA-PKcs deficiency were not rescued in the absence of Rad54, suggesting that they are not mediated by Rad54 activity.