title: Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, USA.
authors.forename: Jungseog
authors.initials: J
authors.lastname: Kang
authors.forename: Jaideep
authors.initials: J
authors.lastname: Chaudhary
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Soonjoung
authors.initials: S
authors.lastname: Kim
authors.forename: Chad A
authors.initials: CA
authors.lastname: Brautigam
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D018360:Crystallography, X-Ray; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D051379:Mice; D008938:Mitosis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D014162:Transfection
chemical_list: C000715594:CBX5 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D034741:RNA, Small Interfering; C496644:SGO1 protein, human; D000090266:Chromobox Protein Homolog 5