Abstract:
:Cellular senescence is an irreversible growth arrest and is presumed to be a natural barrier to tumor development. Like telomere shortening, certain defects in chromosome integrity can trigger senescence; however, the roles of centromere proteins in regulating commitment to the senescent state remains to be established. We examined chromatin structure in senescent human primary fibroblasts and found that CENP-A protein levels are diminished in senescent cells. Senescence-associated reduction of CENP-A is caused by transcriptional and posttranslational control. Surprisingly, forced reduction of CENP-A by short-hairpin RNA was found to cause premature senescence in human primary fibroblasts. This premature senescence is dependent on a tumor suppressor, p53, but not on p16(INK4a)-Rb; the depletion of CENP-A in p53-deficient cells results in aberrant mitosis with chromosome missegregation. We propose that p53-dependent senescence that arises from CENP-A reduction acts as a "self-defense mechanism" to prevent centromere-defective cells from undergoing mitotic proliferation that potentially leads to massive generation of aneuploid cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Maehara K,Takahashi K,Saitoh Sdoi
10.1128/MCB.01318-09subject
Has Abstractpub_date
2010-05-01 00:00:00pages
2090-104issue
9eissn
0270-7306issn
1098-5549pii
MCB.01318-09journal_volume
30pub_type
杂志文章abstract::We have cloned and characterized the gene encoding the late histone H1-beta subtype from the sea urchin Strongylocentrotus purpuratus. The gene contains all of the upstream sequence homologies previously seen in late H1-gamma genes. The expression of H1-beta mRNA is coordinated with that of H1-gamma mRNA, and like H1-...
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pub_type: 杂志文章
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pub_type: 杂志文章
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