title: E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks.
abstract: The E2F1 transcription factor is post-translationally modified and stabilized in response to various forms of DNA damage to regulate the expression of cell cycle and pro-apoptotic genes. E2F1 also forms foci at DNA double-strand breaks (DSBs) but the function of E2F1 at sites of damage is unknown. Here we demonstrate that the absence of E2F1 leads to spontaneous DNA breaks and impaired recovery following exposure to ionizing radiation. E2F1 deficiency results in defective NBS1 phosphorylation and foci formation in response to DSBs but does not affect NBS1 expression levels. Moreover, an increased association between NBS1 and E2F1 is observed in response to DNA damage, suggesting that E2F1 may promote NBS1 foci formation through a direct or indirect interaction at sites of DNA breaks. E2F1 deficiency also impairs RPA and Rad51 foci formation indicating that E2F1 is important for DNA end resection and the formation of single-stranded DNA at DSBs. These findings establish new roles for E2F1 in the DNA damage response, which may directly contribute to DNA repair and genome maintenance.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center; Smithville, TX, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Regina L
authors.initials: RL
authors.lastname: Weaks
authors.forename: Anup K
authors.initials: AK
authors.lastname: Biswas
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Guo
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Li
authors.forename: David G
authors.initials: DG
authors.lastname: Johnson
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004247:DNA / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor / Q000172:deficiency / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C112156:NBN protein, human; C466108:Nijmegen breakage syndrome 1 protein, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051716:Replication Protein A; D004247:DNA; D051135:Rad51 Recombinase