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Title: Structural analysis of a carcinogen-induced genomic rearrangement event

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
; ; ;  [1]
  1. 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