POT1b protects telomeres from end-to-end chromosomal fusions and aberrant homologous recombination
POT1b protects telomeres from end-to-end chromosomal fusions and aberrant homologous recombination
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DOI：
10.1038/sj.emboj.7601294
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发表时间：
2006-11-01
期刊：
影响因子：
11.4
通讯作者：
Chang, Sandy
中科院分区：
文献类型：
--
作者：
He, Hua;Multani, Asha S.;Chang, Sandy
POT1(Protected Of Telomere 1)是一种高度保守的单链端粒结合蛋白，对端粒末端的保护至关重要。在这里，我们报告了老鼠锅家族的第二个成员的克隆和特征。POT1b通过保守的DNA结合寡核苷酸/寡糖(OB)折叠结合端粒DNA。与POT1a相比，POT1b OB-折叠对端粒的序列特异性较低。与POT1a相比，仅含有OB-折叠的截短POT1b在体内可以有效地定位到端粒。一个不能结合端粒DNA的突变的Pot1b等位基因的过度表达引发了端粒的DNA损伤反应，导致了P53依赖的衰老。此外，观察到端粒上30个富含G的悬垂减少，染色体融合增加，同源重组(HR)增加。ShRNA介导的内源性Pot1b缺失导致Pot1a缺陷细胞的染色体畸变率增加。我们的结果表明POT1b在端粒上起着重要的保护作用，适当地维持染色体的稳定性需要这两种POT蛋白。
POT1 (protection of telomere 1) is a highly conserved single-stranded telomeric binding protein that is essential for telomere end protection. Here, we report the cloning and characterization of a second member of the mouse POT family. POT1b binds telomeric DNA via conserved DNA binding oligonucleotide/oligosaccharide (OB) folds. Compared to POT1a, POT1b OB-folds possess less sequence specificity for telomeres. In contrast to POT1a, truncated POT1b possessing only the OB-folds can efficiently localize to telomeres in vivo. Overexpression of a mutant Pot1b allele that cannot bind telomeric DNA initiated a DNA damage response at telomeres that led to p53-dependent senescence. Furthermore, a reduction of the 30 G-rich overhang, increased chromosomal fusions and elevated homologous recombination (HR) were observed at telomeres. shRNA mediated depletion of endogenous Pot1b in Pot1a deficient cells resulted in increased chromosomal aberrations. Our results indicate that POT1b plays important protective functions at telomeres and that proper maintenance of chromosomal stability requires both POT proteins.