Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells.
Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells.
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DOI：
10.1091/mbc.e11-01-0009
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发表时间：
2011-04-15
影响因子：
3.3
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Kang J;Chaudhary J;Dong H;Kim S;Brautigam CA;Yu H
人Shugoshin 1（Sgo 1）在有丝分裂期间保护着丝粒姐妹染色单体凝聚。异染色质蛋白1（HP 1）已被提出招募Sgo 1有丝分裂的着丝粒。我们表明，分子相互作用，针对HP 1有丝分裂着丝粒是不兼容的HP 1进一步招聘Sgo 1。我们的研究结果阐明了着丝粒HP 1在染色体分离中的作用。人Shugoshin 1（Sgo 1）在前期保护着丝粒姐妹染色单体的凝聚力，并防止过早的姐妹染色单体分离。异染色质蛋白1（Heterochromatin protein 1，HP 1）被认为可以通过直接将Sgo 1靶向有丝分裂中的着丝粒来保护着丝粒姐妹染色单体的凝聚力。在这里，我们表明，HP 1 α是针对有丝分裂着丝粒的INCENP，一个亚基的染色体乘客复合体（CPC）。生物化学和结构研究表明，HP 1-INCENP和HP 1-Sgo 1相互作用都需要HP 1染色体阴影结构域与INCENP或Sgo 1中的PXVXL/I基序结合，这表明与INCENP结合的着丝粒HP 1 α不能募集Sgo 1。一致的是，在HP 1结合缺陷的Sgo 1突变体的功能，在着丝粒凝聚力的保护和本地化正常的有丝分裂中的着丝粒。相比之下，INCENP或Sgo 1突变体在HP 1结合缺陷不能定位于着丝粒间期。因此，我们的研究结果表明，HP 1结合INCENP或Sgo 1是不成熟的人细胞有丝分裂过程中的着丝粒凝聚力保护，但可能会调节尚未表征的间期功能的CPC或Sgo 1在着丝粒。
Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during mitosis. Heterochromatin protein 1 (HP1) has been proposed to recruit Sgo1 to mitotic centromeres. We show that the molecular interaction targeting HP1 to mitotic centromeres is incompatible with HP1 further recruiting Sgo1. Our results clarify the role of centromeric HP1 in chromosome segregation. Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres.