title: Regulation of the Nijmegen breakage syndrome 1 gene NBS1 by c-myc, p53             and coactivators mediates estrogen protection from DNA damage in breast cancer             cells.
abstract: In mammalian cells more than 90% of double-strand breaks are repaired by NHEJ. Impairment of this pathway is associated with cell cycle arrest, cell death, genomic instability and cancer. Human diseases such as Nijmegen breakage syndrome, due to mutations in the NBS1 gene, produce defects in resection of double-strand breaks. NBS1 hypomorphic mutant mice are viable, and cells from these mice are defective in S phase and G2/M checkpoints. NBS1 polymorphisms have been associated with increased risk of breast cancer. We previously demonstrated that estradiol protected estrogen receptor (ER)-positive (+) breast cancer cell lines against double-strand breaks and cell death. We now demonstrate that protection from double-strand break damage in ER+ cells is mediated via regulation by c-myc, p53, CBP and SRC1 coactivators in intron 1 of the NBS1 gene. We concluded that NBS1 is responsible for estradiol-mediated protection from double-strand breaks in ER+ breast cancer cells.
authors.affiliation: University of Illinois Cancer Center, Chicago, IL 60612, USA.
authors.forename: Rowena
authors.initials: R
authors.lastname: Wan
authors.forename: Jianchun
authors.initials: J
authors.lastname: Wu
authors.forename: Kaitrin K
authors.initials: KK
authors.lastname: Baloue
authors.forename: David L
authors.initials: DL
authors.lastname: Crowe
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D049932:Nijmegen Breakage Syndrome / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004967:Estrogens; C489427:MYC protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004958:Estradiol