Abstract
Mammalian cells evolve a delicate system, the DNA damage response (DDR) pathway, to monitor genomic integrity and to prevent the damage from both endogenous end exogenous insults. Emerging evidence suggests that aberrant DDR and deficient DNA repair are strongly associated with cancer and aging. Our understanding of the core program of DDR has made tremendous progress in the past two decades. However, the long list of the molecules involved in the DDR and DNA repair continues to grow and the roles of the new “dots” are under intensive investigation. Here, we review the connection between DDR and DNA repair and aging and discuss the potential mechanisms by which deficient DNA repair triggers systemic effects to promote physiological or pathological aging.
Highlights
We witnessed a fruitful DNA damage response and repair year in 2015
Xeroderma pigmentosum (XP) patients exhibited several neurological symptoms such as microcephaly, mental retardation and deafness, which are linked to mutations in genes such as XPA, XPB, XPD, XPF, and XPG that are involved in nucleotide excision repair (NER) [39]
Because the insufficiency of repair will cause the accumulation of DNA damage which leads to cell death or functional defect, it is reasonable to hypothesize that DNA damage response (DDR) and repair is closely associated with aging [47]
Summary
We witnessed a fruitful DNA damage response and repair year in 2015. Elledge for their discoveries of a critical genome protection mechanism, the DNA damage response (DDR) [2]. DNA receives endogenous and exogenous insults every minute and the lesions (approximately 104–105 per cell per day) are extremely deleterious to cells [3]. These lesions, if not correctly repaired, will interrupt genome replication and transcription and cause wide-scale chromosomal aberrations that trigger malignant transformation or cell death. Effective sensing and repair systems are developed during evolution to eliminate the DNA lesions and to maintain genome integrity. Dysregulation of DDR and repair is closely associated with human diseases such as cancers, cardiovascular disease, neurodegenerative disorders and aging [4,5,6,7]
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