GCN5 and E2F1 stimulate nucleotide excision repair by promoting H3K9 acetylation at sites of damage.
Chromatin structure is known to be a barrier to DNA repair and a large number of studies have now identified various factors that modify histones and remodel nucleosomes to facilitate repair. In response to ultraviolet (UV) radiation several histones are acetylated and this enhances the repair of DNA photoproducts by the nucleotide excision repair (NER) pathway. However, the molecular mechanism by which UV radiation induces histone acetylation to allow for efficient NER is not completely understood. We recently discovered that the E2F1 transcription factor accumulates at sites of UV-induced DNA damage and directly stimulates NER through a non-transcriptional mechanism. Here we demonstrate that E2F1 associates with the GCN5 acetyltransferase in response to UV radiation and recruits GCN5 to sites of damage. UV radiation induces the acetylation of histone H3 lysine 9 (H3K9) and this requires both GCN5 and E2F1. Moreover, as previously observed for E2F1, knock down of GCN5 results in impaired recruitment of NER factors to sites of damage and inefficient DNA repair. These findings demonstrate a direct role for GCN5 and E2F1 in NER involving H3K9 acetylation and increased accessibility to the NER machinery.
Department of Molecular Carcinogenesis, UT MD Anderson Cancer Center, Science Park-Research Division, 1808 Park Road 1C, PO Box 389, Smithville, TX 78957, USA.
Ruifeng
R
Guo
Jie
J
Chen
David L
DL
Mitchell
David G
DG
Johnson
D000107:Acetylation; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D050687:E2F1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D014466:Ultraviolet Rays; D050880:p300-CBP Transcription Factors / Q000032:analysis / Q000502:physiology*; D000099224:p300-CBP-Associated Factor
D050687:E2F1 Transcription Factor; D006657:Histones; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493753:E2F1 protein, human