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Curr Opin Genet Dev. 2014 Jun;26:89-95. doi: 10.1016/j.gde.2014.06.009. Epub 2014 Aug 11.

Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing.

Author information

1
IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy.
2
Department of Microbiology and Molecular Genetics, New Jersey Medical School - Cancer Center, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ 07103, USA.
3
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
4
IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy; Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia 27100, Italy. Electronic address: fabrizio.dadda@ifom.eu.

Abstract

The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?

PMID:
25104620
PMCID:
PMC4217147
DOI:
10.1016/j.gde.2014.06.009
[Indexed for MEDLINE]
Free PMC Article

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