Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal

Journal Article · Sun Aug 01 00:00:00 EDT 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.15.7260· OSTI ID:5923857

Parris, C N; Kraemer, K H ^[1]

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1. National Cancer Institute, Bethesda, MD (United States)

The authors compared the contribution to mutagenesis on Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of >200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, the data suggest that prevention of UV-induced skin cancers is associated with proficient repair of nondimer photoproducts. 38 refs., 3 figs., 2 tabs.

• OSTI ID: 5923857
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:15; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GENE MUTATIONS
DNA REPAIR
ULTRAVIOLET RADIATION
GENETIC EFFECTS
CYCLOALKANES
DIMERS
MUTAGENESIS
MUTATION FREQUENCY
PHOTOREACTIVATION
PHOTOSENSITIVITY
XERODERMA PIGMENTOSUM
XP CELLS
ALKANES
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONGENITAL DISEASES
DISEASES
ELECTROMAGNETIC RADIATION
HEREDITARY DISEASES
HYDROCARBONS
MUTATIONS
ORGANIC COMPOUNDS
RADIATIONS
REPAIR
SENSITIVITY
SKIN DISEASES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture