In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. 2003

Maureen E Fitch, and Satoshi Nakajima, and Akira Yasui, and James M Ford
Departments of Medicine and Genetics, Division of Oncology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305, USA.

The initial step in mammalian nucleotide excision repair (NER) of the major UV-induced photoproducts, cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs), requires lesion recognition. It is believed that the heterodimeric proteins XPC/hHR23B and UV-DDB (UV-damaged DNA binding factor, composed of the p48 and p127 subunits) perform this function in genomic DNA, but their requirement and lesion specificity in vivo remains unknown. Using repair-deficient xeroderma pigmentosum (XP)-A cells that stably express photoproduct-specific photolyases, we determined the binding characteristics of p48 and XPC to either CPDs or 6-4PPs in vivo. p48 localized to UV-irradiated sites that contained either CPDs or 6-4PPs. However, XPC localized only to UV-irradiated sites that contained 6-4PPs, suggesting that XPC does not efficiently recognize CPDs in vivo. XPC did localize to CPDs when p48 was overexpressed in the same cell, signifying that p48 activates the recruitment of XPC to CPDs and may be the initial recognition factor in the NER pathway.

UI MeSH Term Description Entries
D007614 Macropodidae A family of herbivorous leaping MAMMALS of Australia, New Guinea, and adjacent islands. Members include kangaroos, wallabies, quokkas, and wallaroos. Kangaroos,Macropus,Petrogale,Quokkas,Setonix,Wallabies,Wallabies, Rock,Wallaroo,Macropus robustus,Kangaroo,Petrogales,Quokka,Rock Wallabies,Rock Wallaby,Wallaby,Wallaby, Rock,Wallaroos
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011740 Pyrimidine Dimers Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION. Cyclobutane Pyrimidine Dimer,Cyclobutane-Pyrimidine Dimer,Cytosine-Thymine Dimer,Pyrimidine Dimer,Thymine Dimer,Thymine Dimers,Cyclobutane-Pyrimidine Dimers,Cytosine-Thymine Dimers,Thymine-Cyclobutane Dimer,Thymine-Thymine Cyclobutane Dimer,Cyclobutane Dimer, Thymine-Thymine,Cyclobutane Dimers, Thymine-Thymine,Cyclobutane Pyrimidine Dimers,Cytosine Thymine Dimer,Cytosine Thymine Dimers,Pyrimidine Dimer, Cyclobutane,Pyrimidine Dimers, Cyclobutane,Thymine Cyclobutane Dimer,Thymine Thymine Cyclobutane Dimer,Thymine-Cyclobutane Dimers,Thymine-Thymine Cyclobutane Dimers
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D004255 Deoxyribodipyrimidine Photo-Lyase An enzyme that catalyzes the reactivation by light of UV-irradiated DNA. It breaks two carbon-carbon bonds in PYRIMIDINE DIMERS in DNA. DNA Photolyase,DNA Photoreactivating Enzyme,Photoreactivating Enzyme,Photoreactivation Enzyme,DNA Photolyases,Deoxyribodipyrimidine Photolyase,Photolyase,Photolyases,Deoxyribodipyrimidine Photo Lyase,Photo-Lyase, Deoxyribodipyrimidine,Photolyase, DNA,Photolyase, Deoxyribodipyrimidine,Photolyases, DNA,Photoreactivating Enzyme, DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections

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