Protein requirements for sister telomere association in human cells
Protein requirements for sister telomere association in human cells
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DOI：
10.1038/sj.emboj.7601903
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发表时间：
2007-11-01
期刊：
影响因子：
11.4
通讯作者：
Smith, Susan
中科院分区：
文献类型：
--
作者：
Canudas, Silvia;Houghtaling, Benjamin R.;Smith, Susan
先前对人类细胞的研究表明，姐妹端粒在有丝分裂时对其分离有不同的要求。在坦科聚合酶 1（一种端粒聚（ADP-核糖）聚合酶）耗尽的细胞中，姐妹染色单体臂和着丝粒正常分离，但端粒仍然相连，细胞在有丝分裂中停滞。在这里，我们使用生化和遗传学方法来识别可能介导姐妹端粒持久关联的蛋白质。我们使用免疫沉淀分析表明，端粒蛋白 TRF1（端锚聚合酶 1 的 PARsylation 受体）和 TIN2（TRF1 结合伴侣）均与粘连蛋白 Scc3 亚基的 SA1 直向同源物结合。蔗糖梯度沉降表明TRF1与SA1-粘连蛋白复合物共沉积。 SA1 粘连蛋白亚基或端粒蛋白（TRF1 和 TIN2）的耗竭可恢复坦科聚合酶 1 耗竭细胞有丝分裂中姐妹端粒的正常分辨率。此外，TRF1 和 TIN2 或 SA1 的消耗消除了有丝分裂进程中对端锚聚合酶 1 的需求。我们的研究表明，人类细胞中的姐妹端粒关联是由粘连蛋白亚基和端粒染色质成分之间的新型关联介导的。
Previous studies in human cells indicate that sister telomeres have distinct requirements for their separation at mitosis. In cells depleted for tankyrase 1, a telomeric poly(ADP- ribose) polymerase, sister chromatid arms and centromeres separate normally, but telomeres remain associated and cells arrest in mitosis. Here, we use biochemical and genetic approaches to identify proteins that might mediate the persistent association at sister telomeres. We use immunoprecipitation analysis to show that the telomeric proteins, TRF1 (an acceptor of PARsylation by tankyrase 1) and TIN2 (a TRF1 binding partner) each bind to the SA1 ortholog of the cohesin Scc3 subunit. Sucrose gradient sedimentation shows that TRF1 cosediments with the SA1 - cohesin complex. Depletion of the SA1 cohesin subunit or the telomeric proteins (TRF1 and TIN2) restores the normal resolution of sister telomeres in mitosis in tankyrase 1- depleted cells. Moreover, depletion of TRF1 and TIN2 or SA1 abrogates the requirement for tankyrase 1 in mitotic progression. Our studies indicate that sister telomere association in human cells is mediated by a novel association between a cohesin subunit and components of telomeric chromatin.