Senescence and Genome dynamics

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Aging is a risk factor for cancer development. Similar to cancer cells, senescing cells often develop genomic instability. These suggest the correlation between cellular senescence, genomic instability, and cancer development. However, it is still elusive, how senescence associates with the elevation of cancer risk. Here, we focused to study (1) possible alteration in genome dynamics regulation during senescing process and (2) possible genomic maintenance in senescing cells.

The most frequent genomic instabilities in cancer cells are the aberration in the chromosome number, i.e., aneuploidy and tetraploidy. We recently reported that aberrant growth stimulation in senescing cells, which acts as like oncogene accelerations, induces DNA replication stress and the resulting DNA lesions that are carried over into the M phase, followed by cells fail to terminate cytokinesis and generate tetraploidy prior to the development of immortality (Ichijima et al., 2010). This suggests the fragility in senescing genome. We currently promote following investigations: (1) the possible reasons of fragility in senescing genome; (2) the association between microsatellite instability and senescence; (3) the correlation between mutation and genomic instability; (4) the effects of genome dynamics on cell death and on cellular senescence by DNA damaging anti-cancer agents for the possible application in cancer therapy.