Enhanced UV-induced mutagenesis in the UV61 cell line, the Chinese hamster homologue of Cockayne's syndrome B, is associated with defective transcription coupled repair of cyclobutane pyrimidine dimers. 1998

M P Vreeswijk, and M W Overkamp, and B E Westland, and S van Hees-Stuivenberg, and H Vrieling, and M Z Zdzienicka, and A A van Zeeland, and L H Mullenders
MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, Netherlands.

Cells from Cockayne's syndrome (CS) patients are hypersensitive to the cytotoxic effects of UV-irradiation and are defective in transcription coupled repair (TCR). We have examined the mutagenic consequences of impaired TCR in the Chinese hamster cell line UV61, the rodent homologue of CS complementation group B. Analysis of the two major UV-induced photolesions, cyclobutane pyrimidine dimers (CPD) and pyrimidine 6-4 pyrimidone photoproducts (6-4 PP), revealed that repair of CPD from the transcribed strand was strongly reduced in UV61 cells, but repair of 6-4 PP was indistinguishable from that in wild-type hamster cells. UV-induced mutation induction was enhanced in UV61 compared to that observed in repair proficient cells. The spectrum of UV-induced base substitutions in UV61 was clearly different from that observed in wild-type hamster cells and resembled the spectrum previously observed in nucleotide excision repair deficient hamster cells. In UV61 cells a strong strand bias for mutation induction was found; assuming that premutagenic lesions occur at dipyrimidine sequences, 76% of the mutations could be attributed to lesions in the transcribed strand. These data strongly favour the hypothesis that defective TCR of CPD is responsible for the enhanced UV-induced mutagenesis in UV61 cells.

UI MeSH Term Description Entries
D007041 Hypoxanthine Phosphoribosyltransferase An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8. Guanine Phosphoribosyltransferase,HPRT,Hypoxanthine-Guanine Phosphoribosyltransferase,IMP Pyrophosphorylase,HGPRT,HPRTase,Hypoxanthine Guanine Phosphoribosyltransferase,Phosphoribosyltransferase, Guanine,Phosphoribosyltransferase, Hypoxanthine,Phosphoribosyltransferase, Hypoxanthine-Guanine,Pyrophosphorylase, IMP
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
D011836 Radiation Tolerance The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS. Radiation Sensitivity,Radiosensitivity,Sensitivity, Radiation,Tolerance, Radiation,Radiation Sensitivities,Radiation Tolerances,Radiosensitivities,Sensitivities, Radiation,Tolerances, Radiation
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003057 Cockayne Syndrome A syndrome characterized by multiple system abnormalities including DWARFISM; PHOTOSENSITIVITY DISORDERS; PREMATURE AGING; and HEARING LOSS. It is caused by mutations of a number of autosomal recessive genes encoding proteins that involve transcriptional-coupled DNA REPAIR processes. Cockayne syndrome is classified by the severity and age of onset. Type I (classical; CSA) is early childhood onset in the second year of life; type II (congenital; CSB) is early onset at birth with severe symptoms; type III (xeroderma pigmentosum; XP) is late childhood onset with mild symptoms. Progeria-Like Syndrome,Cockayne Syndrome Type 3,Cockayne Syndrome Type C,Cockayne Syndrome, Group A,Cockayne Syndrome, Group B,Cockayne Syndrome, Group C,Cockayne Syndrome, Type A,Cockayne Syndrome, Type B,Cockayne Syndrome, Type C,Cockayne Syndrome, Type I,Cockayne Syndrome, Type II,Cockayne Syndrome, Type III,Dwarfism-Retinal Atrophy-Deafness Syndrome,Group A Cockayne Syndrome,Group B Cockayne Syndrome,Group C Cockayne Syndrome,Progeroid Nanism,Type A Cockayne Syndrome,Type B Cockayne Syndrome,Type C Cockayne Syndrome,Type I Cockayne Syndrome,Type II Cockayne Syndrome,Type III Cockayne Syndrome,Progeria Like Syndrome,Progeria-Like Syndromes,Syndrome, Cockayne,Syndrome, Progeria-Like
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds 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
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
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

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