title: A novel role for the condensin II complex in cellular senescence.
abstract: Although cellular senescence is accompanied by global alterations in genome architecture, how the genome is restructured during the senescent processes is not well understood. Here, we show that the hCAP-H2 subunit of the condensin II complex exists as either a full-length protein or an N-terminus truncated variant (ΔN). While the full-length hCAP-H2 associates with mitotic chromosomes, the ΔN variant exists as an insoluble nuclear structure. When overexpressed, both hCAP-H2 isoforms assemble this nuclear architecture and induce senescence-associated heterochromatic foci (SAHF). The hCAP-H2ΔN protein accumulates as cells approach senescence, and hCAP-H2 knockdown inhibits oncogene-induced senescence. This study identifies a novel mechanism whereby condensin drives senescence via nuclear/genomic reorganization.
authors.affiliation: a The Wistar Institute ; Philadelphia , PA USA.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Hengrui
authors.initials: H
authors.lastname: Zhu
authors.forename: Rugang
authors.initials: R
authors.lastname: Zhang
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Noma
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D001483:Base Sequence; D016922:Cellular Senescence / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; C472564:PRSS27 protein, human; D012697:Serine Endopeptidases; D000251:Adenosine Triphosphatases
keywords: BrdU, bromodeoxyuridine; CDK, cyclin dependent kinase; DAPI, 4,6-diamidino-2-phenylindole; NCAPH2, non-SMC chromosome-associated protein H2 gene; RPE-1, hTERT-immortalized retinal pigment epithelial cell line; Rb, retinoblastoma protein; SA-β-gal, senescence-associated β-galactosidase; SADS, senescence-associated distension of satellites; SAHF; SAHF, senescence-associated heterochromatic foci; SMC, structural maintenance of chromosomes; cellular senescence; condensin; genome organization; hCAP-H2, human chromosome-associated protein H2; hTERT, human telomerase reverse transcriptase; human; nuclear architecture; oncogene-induced senescence; shRNA, short-hairpin RNA.; uORF, upstream open reading frame