Research Perspective Volume 3, Issue 10 pp 943—954
‘Relax and Repair’ to restrain aging
- 1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong
- 2 Cancer Science Institute of Singapore, National University of Singapore, Singapore
- 3 Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China
received: October 21, 2011 ; accepted: October 29, 2011 ; published: October 30, 2011 ;https://doi.org/10.18632/aging.100399
How to Cite
The maintenance of genomic integrity requires the precise identification and repair of DNA damage. Since DNA is packaged and condensed into higher order chromatin, the events associated with DNA damage recognition and repair are orchestrated within the layers of chromatin. Very similar to transcription, during DNA repair, chromatin remodelling events and histone modifications act in concert to ‘open’ and relax chromatin structure so that repair proteins can gain access to DNA damage sites. One such histone mark critical for maintaining chromatin structure is acetylated lysine 16 of histone H4 (AcH4K16), a modification that can disrupt higher order chromatin organization and convert it into a more ‘relaxed’ configuration. We have recently shown that impaired H4K16 acetylation delays the accumulation of repair proteins to double strand break (DSB) sites which results in defective genome maintenance and accelerated aging in a laminopathy-based premature aging mouse model. These results support the idea that epigenetic factors may directly contribute to genomic instability and aging by regulating the efficiency of DSB repair. In this article, the interplay between epigenetic misregulation, defective DNA repair and aging is discussed.
DSB: double strand break; AcH4K16: acetylated lysine 16 of histone H4; IRIF: irradiation-induced foci; HR: homologous recombination; NHEJ: non-homologous end joining; HAT: histone acetyltransferase; HDAC: histone deacetylase; MEF: mouse embryonic fibroblast; HGPS: Hutchinson Gilford progeria syndrome; IR: Irradiation; AT: Ataxia-telangiectasia.