Zhang Haitao, Audry Julien, Runge Kurt W
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, 44195 USA.
Present address: Nexelis, 525 Bd Cartier O, Laval, QC H7V 3S8, Canada.
bioRxiv. 2025 May 1:2025.05.01.651670. doi: 10.1101/2025.05.01.651670.
We have formed new short telomeres in using an inducible nuclease that cuts near telomere repeats in cells that lack, cannot recruit or cannot fully activate telomerase. Sequencing these new telomeres showed that cells can divide at least 4 times with ~30 bp of non-telomeric sequence at the chromosome end in cells lacking telomerase, which contrasts with current models for the roles of terminal single-stranded telomere repeats and the telomere proteins in telomere protection and replication. Cells that cannot recruit or activate telomerase had similar results, with additional rearrangements or telomere repeat addition, respectively.
我们通过使用一种可诱导的核酸酶，在缺乏、无法招募或无法完全激活端粒酶的细胞中，在靠近端粒重复序列处进行切割，从而形成了新的短端粒。对这些新端粒进行测序表明，在缺乏端粒酶的细胞中，细胞能够以染色体末端约30个碱基对的非端粒序列至少分裂4次，这与目前关于末端单链端粒重复序列和端粒蛋白在端粒保护和复制中作用的模型形成对比。无法招募或激活端粒酶的细胞分别有类似的结果，伴有额外的重排或端粒重复序列添加。
