Abstract
Many of the biochemical details of nucleotide excision repair (NER) have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.
Highlights
Preserving the integrity of genetic information encoded in our genome in order for it to be passed from generation to generation presents a major challenge
GCN5 is important for GG-nucleotide excision repair (NER) by controlling histone H3K9 acetylation [75,76,77]. These findings suggest that like p53, E2F1 functions as an accessibility factor for NER by recruiting GCN5 to sites of damage and helping to remodel chromatin by promoting H3K9 acetylation and perhaps other histone modifications
E2F1 and p53 function as sequence-specific transcription factors and as chromatin accessibility factors for NER adds to the growing list of proteins found to play dual roles in transcription and repair
Summary
Preserving the integrity of genetic information encoded in our genome in order for it to be passed from generation to generation presents a major challenge. Regulating access to the genome through chromatin remodeling encompasses a variety of enzymatic activities and processes such as histone acetylation, methylation, phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, and SUMOylation, as well as DNA methylation. These modifications may lead to nucleosome repositioning, eviction and incorporation [4,5,6,7]. Given that transcription and DNA repair both involve the manipulation of DNA in the context of chromatin, it is perhaps not surprising that there is considerable overlap between proteins regulating these two processes. E2F1, and their non-transcriptional functions in stimulating nucleotide excision repair (NER) in mammalian cells
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