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PMID:16545529

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Citation

Wei, Y, Lin-Lee, YC, Yang, X, Dai, W, Zhao, S, Rassool, FV, Elgart, GW, Feun, L, Savaraj, N and Kuo, MT (2006) 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. Gene 372:44-52

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 approximately 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.

Links

PubMed Online version:10.1016/j.gene.2005.12.024

Keywords

Adipocytes/cytology; Adipogenesis/genetics; Amino Acid Sequence; Animals; Base Sequence; Cell Differentiation; Cells, Cultured; Chromosome Fragile Sites/genetics; Chromosomes, Mammalian/genetics; Cloning, Molecular; Conserved Sequence/genetics; Cricetinae; Cricetulus; DNA, Complementary/genetics; Gene Amplification/genetics; Genes, MDR/genetics; Genome; Humans; Male; Mitosis; Molecular Sequence Data; Open Reading Frames/genetics; RNA, Messenger/genetics; RNA, Messenger/metabolism; Spermatocytes/cytology; Spermatogenesis/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:K1109

involved_in

GO:0045444: fat cell differentiation

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0051647: nucleus localization

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0019915: lipid storage

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

located_in

GO:0005634: nucleus

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0060612: adipose tissue development

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0001558: regulation of cell growth

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0006629: lipid metabolic process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:K1109

involved_in

GO:0007283: spermatogenesis

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete


See also

References

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