Role of cyclin B1 levels in DNA damage and DNA damage-induced senescence. 2013

Yuji Nakayama, and Naoto Yamaguchi
Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan. nakayama@mb.kyoto-phu.ac.jp

The cyclin B1-Cdk1 complex is a key regulator of mitotic entry. A large number of proteins are phosphorylated by the cyclin B1-Cdk1 complex prior to mitotic entry. Regulation of the mitotic events is linked to the control of the activity of the cyclin B1-Cdk1 complex to make cells enter mitosis, arrest at G2-phase, or skip mitosis. The roles of cyclin B1 levels in DNA damage are described. The ATM/ATR pathway acts as a molecular switch for regulating cell fates, flipping between cell death via progress into mitosis and polyploidization via sustained G2 arrest upon DNA damage, where cyclin B1 degradation is important for inducing polyploidization. The decrease in cyclin B1 levels that is induced by DNA damage leads to polyploidization in DNA damage-induced senescence. A useful method for monitoring the expression level of cyclin B1 throughout cell cycle progression in living cells is also presented.

UI MeSH Term Description Entries
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D011123 Polyploidy The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc. Polyploid,Polyploid Cell,Cell, Polyploid,Cells, Polyploid,Polyploid Cells,Polyploidies,Polyploids
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016922 Cellular Senescence Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS. Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D056744 Cyclin B1 A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

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