Structural analysis of a carcinogen-induced genomic rearrangement event
- Children's Hospital, Philadelphia, PA (United States) Univ. of Pennsylvania, Philadelphia (United States)
The authors have explored the mechanism of genomic rearrangement in a hamster fibroblast cell culture system in which rearrangements are induced 5{prime} to the endogenous thymidine kinase gene by chemical carcinogen treatment. The wild-type region around one rearrangement breakpoint was cloned and sequenced. With this sequence information, the carcinogen-induced rearrangement was cloned from the corresponding rearranged cell line by the inverse polymerase chain reaction. After the breakpoint fragment was sequenced, the wild-type rearrangement partner (RP15) was isolated by a second inverse polymerase chain reaction of unrearranged DNA. Comparison of the sequence of the rearrangement breakpoint with the wild-type RP15 and 5{prime} thymidine kinase gene regions revealed short repeats directly at the breakpoint, as well as nearby A+T-rich regions in rearrangement partner. Therefore, these studies reveal interesting sequence and chromatin features near the rearrangement breakpoints and suggest a role for nuclear organization in the mechanism of carcinogen-induced genomic rearrangement.
- OSTI ID:
- 5551254
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:3; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHROMOSOMAL ABERRATIONS
DNA SEQUENCING
NITROSO COMPOUNDS
GENETIC EFFECTS
CARCINOGENS
ELECTROPHORESIS
FIBROBLASTS
HAMSTERS
PHOSPHOTRANSFERASES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
CONNECTIVE TISSUE CELLS
ENZYMES
MAMMALS
MUTATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RODENTS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology