E2F1 localizes to sites of UV-induced DNA damage to enhance nucleotide excision repair.
The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in the DNA damage response is less clear. Using a local UV irradiation technique and immunofluorescence staining, E2F1 is shown to accumulate at sites of DNA damage. Localization of E2F1 to UV-damaged DNA requires the ATM and Rad3-related (ATR) kinase and serine 31 of E2F1 but not an intact DNA binding domain. E2F1 deficiency does not appear to affect the expression of nucleotide excision repair (NER) factors, such as XPC and XPA. However, E2F1 depletion does impair the recruitment of NER factors to sites of damage and reduces the efficiency of DNA repair. E2F1 mutants unable to bind DNA or activate transcription retain the ability to stimulate NER. These findings demonstrate that E2F1 has a direct, non-transcriptional role in DNA repair involving increased recruitment of NER factors to sites of damage.
Guo
Ruifeng
R
Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, Texas 78957, USA.
Chen
Jie
J
Zhu
Feng
F
Biswas
Anup K
AK
Berton
Thomas R
TR
Mitchell
David L
DL
Johnson
David G
DG
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D050687:E2F1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016160:Retinoblastoma Protein / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D002843:Chromatin; D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D012694:Serine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases