title: 'Relax and Repair' to restrain aging.
abstract: 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.
authors: Department of Biochemistry, The University of Hong Kong.
authors: Vaidehi
authors: V
authors: Krishnan
authors: Baohua
authors: B
authors: Liu
authors: Zhongjun
authors: Z
authors: Zhou
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011371:Progeria / Q000235:genetics / Q000503:physiopathology; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A; D006655:Histone Deacetylases