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De novo ‐generated small palindromes are characteristic of amplicon boundary junction of double minutes
Author(s) -
Zhu Jing,
Yu Yang,
Meng Xiangning,
Fan Yihui,
Zhang Yu,
Zhou Chunshui,
Yue Zhichao,
Jin Yan,
Zhang Chunyu,
Yu Lisa,
Ji Wei,
Jia Xueyuan,
Guan Rongwei,
Wu Jie,
Yu Jingcui,
Bai Jing,
Guan XinYuan,
Wang Mingrong,
Lee KiYoung,
Sun Wenjing,
Fu Songbin
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28084
Subject(s) - amplicon , palindrome , biology , palindromic sequence , locus (genetics) , genetics , breakpoint , polymerase chain reaction , microbiology and biotechnology , gene , genome , chromosome
Double minutes (DMs) are hallmarks of gene amplification. However, their molecular structure and the mechanisms of formation are largely unknown. To elucidate the structure and underlying molecular mechanism of DMs, we obtained and cloned DMs using microdissection; and degenerated oligonucleotide primed polymerase chain reaction (DOP‐PCR) from the ovarian cancer cell line UACC‐1598. Two large amplicons, the 284 kb AmpMYCN, originating from locus 2p24.3 and the 391 kb AmpEIF5A2, from locus 3q26.2, were found co‐amplified on the same DMs. The two amplicons are joined through a complex 7 kb junction DNA sequence. Analysis of the junction has revealed three de novo created small palindromes surrounding the six breakpoints. Consistent with these observations, we further found that 70% of the 57 reported DM junction sequences have de novo creation of small palindromic sequences surrounding the breakpoints. Together, our findings indicate that de novo ‐generated small palindromic sequences are characteristic of amplicon boundary junctions on DMs. It is possible that the de novo ‐generated small palindromic sequences, which may be generated through non‐homologous end joining in concert with a novel DNA repair machinery, play a common role in amplicon rejoining and gene amplification.