PDF(Pubmed)
Abstract：
Alternative lengthening of telomeres (ALTs) mechanism is activated in some somatic, germ cells, and human cancer cells. However, the key regulators and mechanisms of the ALT pathway remain elusive. Here we demonstrated that ZBTB40 is a novel telomere-associated protein and binds to telomeric dsDNA through its N-terminal BTB (BR-C, ttk and bab) or POZ (Pox virus and Zinc finger) domain in ALT cells. Notably, the knockout or knockdown of ZBTB40 resulted in the telomere dysfunction-induced foci and telomere lengthening in the ALT cells. The results also show that ZBTB40 is associated with ALT-associated promyelocytic leukemia nuclear bodies, and the loss of ZBTB40 induces the accumulation of the ALT-associated promyelocytic leukemia nuclear bodies in U2OS cells. Taken together, our results implicate that ZBTB40 is a key player of telomere protection and telomere lengthening regulation in human ALT cells.
摘要：
端粒（ALT）机制的替代延长在一些体细胞被激活，生殖细胞,和人类癌细胞。然而,ALT途径的关键调节因子和机制仍然难以捉摸。在这里，我们证明ZBTB40是一种新型的端粒相关蛋白，并通过其在ALT细胞中的N端BTB结构域与端粒dsDNA结合。值得注意的是,ZBTB40的敲除或敲低导致ALT细胞中端粒功能障碍诱导的病灶(TIF)和端粒延长。结果还显示ZBTB40与ALT相关的早幼粒细胞白血病(PML)核体(APB)相关,并且ZBTB40的缺失诱导APB在U2OS细胞中的积累。一起来看,我们的结果提示ZBTB40是人ALT细胞端粒保护和端粒延长调节的关键因素。
