title: The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts.
abstract: The tumor suppressor protein p53 functions in many cellular responses to UV-induced DNA damage, including activating the global nucleotide excision repair (NER) pathway. A potential mechanism for the effect on NER is through the ability of p53 to transcriptionally regulate genes that are directly involved in NER. DDB2 is one such gene that is regulated by p53 at both the basal and UV inducible levels. In order to further understand p53's role in NER, we transfected and selected clones that stably overexpress DDB2 in a human p53 deficient cell line. Global genomic repair (GGR) of cyclobutane pyrimidine dimers was significantly increased in the DDB2 expressing cells in comparison to controls, demonstrating that p53 wt protein itself is not directly required for efficient GGR. The protein product of DDB2, p48, is also post-translationally regulated by proteasomal degradation in response to UV irradiation. The regulation of p48 at both the transcriptional level by p53, and post-translationally by the proteasome suggests that p48 may be a rate limiting component of NER.
authors.affiliation: Departments of Medicine and Genetics, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Fitch
authors.forename: Irina V
authors.initials: IV
authors.lastname: Cross
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Shanthi
authors.initials: S
authors.lastname: Adimoolam
authors.forename: Cindy X
authors.initials: CX
authors.lastname: Lin
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Williams
authors.forename: James M
authors.initials: JM
authors.lastname: Ford
mesh_terms: D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers