Role of nucleotide excision repair proteins in oxidative DNA damage repair: an updating
ABSTRACT DNA repair is a crucial factor in maintaining a low steady-state level of oxidative DNA damage. Base excision repair (BER)
has an important role in preventing the deleterious effects of oxidative DNA damage, but recent evidence points to the involvement
of several repair pathways in this process. Oxidative damage may arise from endogenous and exogenous sources and may target
nuclear and mitochondrial DNA as well as RNA and proteins. The importance of preventing mutations associated with oxidative
damage is shown by a direct association between defects in BER (i.e. MYH DNA glycosylase) and colorectal cancer, but it is
becoming increasingly evident that damage by highly reactive oxygen species plays also central roles in aging and neurodegeneration.
Mutations in genes of the nucleotide excision repair (NER) pathway are associated with diseases, such as xeroderma pigmentosum
and Cockayne syndrome, that involve increased skin cancer risk and/or developmental and neurological symptoms. In this review
we will provide an updating of the current evidence on the involvement of NER factors in the control of oxidative DNA damage
and will attempt to address the issue of whether this unexpected role may unlock the difficult puzzle of the pathogenesis
of these syndromes.
Key wordsoxidative damage–DNA repair–oxidative metabolism–xeroderma pigmentosum–Cockayne syndrome
Article: Oxidative stress during mitochondrial biogenesis compromises mtDNA integrity in growing hearts and induces a global DNA repair response.[show abstract] [hide abstract]
ABSTRACT: Cardiomyocyte development in mammals is characterized by a transition from hyperplastic to hypertrophic growth soon after birth. The rise of cardiomyocyte cell mass in postnatal life goes along with a proportionally bigger increase in the mitochondrial mass in response to growing energy requirements. Relatively little is known about the molecular processes regulating mitochondrial biogenesis and mitochondrial DNA (mtDNA) maintenance during developmental cardiac hypertrophy. Genome-wide transcriptional profiling revealed the activation of transcriptional regulatory circuits controlling mitochondrial biogenesis in growing rat hearts. In particular, we detected a specific upregulation of factors involved in mtDNA expression and translation. More surprisingly, we found a specific upregulation of DNA repair proteins directly linked to increased oxidative damage during heart mitochondrial biogenesis, but only relatively minor changes in the mtDNA replication machinery. Our study paves the way for improved understanding of mitochondrial biogenesis, mtDNA maintenance and physiological adaptation processes in the heart and provides the first evidence for the recruitment of nucleotide excision repair proteins to mtDNA in cardiomyocytes upon DNA damage.Nucleic Acids Research 04/2012; 40(14):6595-607. · 8.03 Impact Factor