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Published online 2 February 2004

Nucleic Acids Research, 2004, Vol. 32, No. 2 749-756
© 2004 Oxford University Press

Structure of a palindromic amplicon junction implicates microhomology-mediated end joining as a mechanism of sister chromatid fusion during gene amplification

Yukiko Okuno, Peter J. Hahn1 and David M. Gilbert*

Department of Biochemistry and Molecular Biology and 1 Department of Radiation Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA

*To whom correspondence should be addressed. Tel: +1 315 464 8723; Fax: +1 315 464 8750; Email: gilbertd{at}upstate.edu
Present address:
Yukiko Okuno, Division of Biological Science, Graduate School of Science, Nagoya University, Huro-Cho, Chikusa-ku, Nagoya, Aichi-pref. 464-8602 Japan

Amplification of the copy number of oncogenes is frequently associated with tumor progression. Often, the amplified DNA consists of large (tens to hundreds of kilobases) ‘head-to-head’ inverted repeat palindromes (amplicons). Several mechanisms have been proposed to explain palindrome formation but their relative contributions in nature have been difficult to assess without precise knowledge of the sequences involved at the junction of natural amplicons. Here, we have sequenced one such junction and compared this sequence to the un-rearranged structure, allowing us to pinpoint the site of sister chromatid fusion. Our results support a novel model, consistent with all described sister chromatid fusions, in which sister chromatid fusion is initiated by microhomology-mediated end joining of double strand breaks.


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