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PMID: 12060719 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Short inverted repeats initiate gene amplification through the formation of a large DNA palindrome in mammalian cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 13 ·2002-06-25 ·Pages 8772-7

Tanaka H, Tapscott SJ, Trask BJ, Yao MC

Abstract

Gene amplification is a common form of genomic instability in a wide variety of organisms and is often associated with tumor progression in mammals. One striking feature of many amplified genes is their organization as large inverted duplications (palindromes). Here, we describe a molecular mechanism for palindrome formation in mammalian cells that is also conserved in protists. We introduced a short (79 or 229 bp) inverted repeat into the genome of Chinese hamster ovary cells and showed that it promoted the formation of a large DNA palindrome after an adjacent DNA double-strand break. This finding suggests that short inverted repeats in the mammalian genome can have a critical role in the initiation of gene amplification. This specific mechanism may provide a novel target for cancer therapies.

MeSH Terms
Animals Base Sequence Blotting, Southern CHO Cells Cricetinae DNA/genetics Gene Amplification Molecular Sequence Data Tetrahydrofolate Dehydrogenase/genetics
Chemicals
DNA Tetrahydrofolate Dehydrogenase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tanaka Hisashi
Division of Basic Sciences and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Tapscott Stephen J
Trask Barbara J
Yao Meng-Chao
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.132275999
Published
2002-06-25
Epub
2002-00-11
Pages
8772-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC124374
Subset
IM
Grants
NIAMS NIH HHS · R01AR45203 · United States
NIGMS NIH HHS · R01GM26210 · United States
NIAMS NIH HHS · R01 AR045203 · United States
NIAMS NIH HHS · R01AR45113 · United States
NIGMS NIH HHS · R01 GM026210 · United States
NIAMS NIH HHS · R01 AR045113 · United States
External Links
PubMed source DOI: 10.1073/pnas.132275999 PMC Full Text View journal details
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