Molecular cloning of Chinese hamster 1q31 chromosomal fragile site DNA that is important to mdr1 gene amplification reveals a novel gene whose expression is associated with spermatocyte and adipocyte differentiation

Yingjie Wei, Yen Chiu Lin-Lee, Xinlin Yang, Wenping Dai, Sheng Zhao, Feyruz V. Rassool, George W. Elgart, Lynn Feun, Niramol Savaraj, M. Tien Kuo

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

DNA amplification plays important roles in the development of drug resistance and tumor progression. One mechanism of DNA amplification involves the breakage-fusion-bridge (BFB) cycle. We previously reported that in Chinese hamster ovary (CHO) cell line, breakage at fragile site 1q31 was associated with mdr1 gene amplification through the BFB mechanism. To elucidate the molecular basis of BFB-mediated DNA amplification, we cloned 1q31 fragile site DNA from a Chinese hamster cell line containing an integrated neomycin-resistance marker. Sequence analyses revealed many characteristics similar to those in other common fragile sites. Moreover, this fragile site contains an evolutionarily conserved novel gene, designated fragile site-associated (FSA) gene. FSA encodes a ∼16-kb mRNA, from which an unusually large open reading frame (orf) of 5005 amino acids can be deduced. The C-terminal portion of FSA shares a striking sequence similarity to that of Caenorhabditi elegans lipid depleted-3 (lpd-3) gene whose function has been demonstrated to involve in lipid storage. We also demonstrated that expression of FSA is associated with the developmental programs of spermatogenesis and adipogenesis. Our results suggest that the Chinese hamster 1q31 fragile site has many important functions including regulation of mdr1 amplification and differentiation of adipocytes and spermatocytes.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalGene
Volume372
Issue number1-2
DOIs
StatePublished - May 10 2006

Keywords

  • Cell growth and differentiation
  • Novel gene
  • Positional cloning
  • Postmitotic regulation

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Molecular cloning of Chinese hamster 1q31 chromosomal fragile site DNA that is important to mdr1 gene amplification reveals a novel gene whose expression is associated with spermatocyte and adipocyte differentiation'. Together they form a unique fingerprint.

  • Cite this