Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids
- Michigan State Univ., East Lansing (United States)
Xeroderma pigmentosum (XP) variant patients show the clinical characteristics of the disease, with increased frequencies of skin cancer, but their cells have a normal, or nearly normal, rate of nucleotide excision repair of UV-induced DNA damage and are only slightly more sensitive than normal cells to the cytotoxic effect of UV radiation. However, they are significantly more sensitive to its mutagenic effect. To examine the mechanisms responsible for this hypermutability, the authors transfected an XP variant cell line with a UV-irradiated (at 254 nm) shuttle vector carrying the {sup F} gene as a target for mutations, allowed replication of the plasmid, determined the frequency and spectrum of mutations induced, and compared the results with those obtained previously when irradiated plasmids carrying the same target gene replicated in a normal cell line. The frequency of mutants increased linearly with dose, but with a slope 5 times steeper than that seen with normal cells. Sequence analysis of the {sup F} gene showed that 52 of 53 independent mutants generated in the XP variant cells contained base substitutions, with 62 of 64 of the substitutions involving a dipyrimidine.
- OSTI ID:
- 5815968
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:17; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA REPAIR
MOLECULAR BIOLOGY
XP CELLS
BIOLOGICAL RADIATION EFFECTS
AMP
DNA REPLICATION
EXTREME ULTRAVIOLET RADIATION
MUTATION FREQUENCY
PLASMIDS
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CONSTITUENTS
ELECTROMAGNETIC RADIATION
NUCLEIC ACID REPLICATION
NUCLEOTIDES
ORGANIC COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
ULTRAVIOLET RADIATION
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture