Skip to main content

Advertisement

Log in

CAND3: A ubiquitously expressed gene immediately adjacent and in opposite transcriptional orientation to the ATM gene at 1lq23.1

  • Original Contribution
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Using a magnetic beads-mediated cDNA selection procedure and a fetal brain expression library, we identified a transcriptional unit within a cosmid positive for the marker D11S384. Pursuit of its full-length cDNA led to the cloning of the third candidate gene (CAND3) we studied in our quest for the ataxiatelangiectasia (A-T) gene, ATM. CAND3 spans ~140 kb of genomic DNA and is located immediately centrimeric to ATM, with 544 bp of DNA separating the two genes. CAND3 encodes two ubiquitously expressed transcripts of ~5.8 kb and ~4.6 kb that are divergently transcribed from a promoter region common to ATM. Nucleotide sequence was determined for one of its alternately spliced transcripts. The predicted protein has 1175 amino acids and is novel in sequence, with only weak homologies to transcriptional factors, nucleoporin protein, and protein kinases, including members of the phosphatidylinositol 3-kinase (PI-3 kinase) family. Although neither homology to ATM nor any mutation of CAND3 in A-T patients has been found, the head-to-head arrangement of CAND3 and ATM, with expression of both housekeeping genes from a common stretch of 544 bp intergenic DNA, suggests a bi-directional promoter possibly for co-regulation of biologically related functions. YACs, BACs, cosmids, and STSs are defined to aid in the further study of this gene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990). Basic local alignment search tool. J Mol Biol 215, 403–410

    PubMed  CAS  Google Scholar 

  • Buckler AJ, Chang DD, Graw SL, Brook JD, Haber DA, Sharp PA, Housman DE (1991). Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. Proc Natl Acad Sci USA 88, 4005–4009

    Article  PubMed  CAS  Google Scholar 

  • Byrd PJ, McConville CM, Cooper P, Parkhill J, Stankovic T, McGuire GM, Thick JA, Taylor AMR (1996). Mutations revealed by sequencing the 5′ half of the gene for ataxia telangiectasia. Hum Mol Genet 5, 145–149

    Article  PubMed  CAS  Google Scholar 

  • Cross SH, Charlton JA, Nan X, Bird AP (1994). Purification of CpG islands using a methylated DNA binding column. Nature Genet 6, 236–244

    Article  PubMed  CAS  Google Scholar 

  • Feinberg AP, Vogelstein BA (1984). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity: addendum Anal Biochem 137, 266–267

    Article  PubMed  CAS  Google Scholar 

  • Frohamn M, Dush M, Martin G (1988). Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci USA 85, 8998–9002

    Article  Google Scholar 

  • Fukao T, Yamaguchi S, Kano M, Orii T, Fujiki Y, Osumi T, Hashimoto T (1990). Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency. J Clin Invest 86, 2086–2092

    Article  PubMed  CAS  Google Scholar 

  • Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NGJ, Lange K, Lathrop GM, Leppert M, Nakamura Y, O’Connell P, Paterson M, Salser W, Sanal O, Silver J, Sparkes RS, Susi E, Weeks DE, Wei S, White R, Yoder F (1988). Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature 336, 577–580

    Article  PubMed  CAS  Google Scholar 

  • Gatti RA, Lange E, Rotman G, Chen X, Uhrhammer N, Polikow J, Liang T, Chiplunkar S, Yang L, Udar N, Dandekar S, Sheikhavandi S, Wang Z, Yang HM, Polikow J, Elasshoff M, Teletar M, Sanal O, Chessa L, McConville C, Taylor M, Shiloh Y, Porras O, Borresen AL, Wegner RD, Curry C, Gerken S, Lange K, Concannon P (1994). Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to a ~850 kb region on chromosome 11Q23.1. Int J Radiat Biol 66, 57–62

    Article  Google Scholar 

  • Gavalas A, Dixon JE, Braytin KA, Zalkin H (1993). Co-expression of two closely linked avian genes for purine nucleotide synthesis from a bidirectional promoter. Mol Cell Biol 13, 4784–4792

    PubMed  CAS  Google Scholar 

  • Genetics Computer Group (April 1991). Program Manual for the GCG Package, Version 7. 575 Science Drive, Madison, Wisconsin, USA 53711

    Google Scholar 

  • Heikkila P, Soininen R, Tryggvason K (1993). Directional regulatory activity of cis-acting elements in the bidirectional al (IV) and a2 (IV) collagen gene promoter. J Biol Chem 268, 24677–24682

    PubMed  CAS  Google Scholar 

  • Hofmann K, Stoffel W (1993). TMBASE-A database of membrane spanning protein segments. Biol Chem 374, 166

    Google Scholar 

  • Imai T, Yamauchi M, Seki N, Saito T, Matsuda Y, Itoh H, Nagase T, Nomura N, Hori T (1996). Identification and characterization of a new gene physically linked to the ATM gene. Genome Res 6, 439–447

    Article  PubMed  CAS  Google Scholar 

  • Kano M, Fukao T, Yamaguchi S, Orri T, Osumi T, Hashimoto T (1991). Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene. Gene 109, 285–290

    Article  PubMed  CAS  Google Scholar 

  • Korn B, Sedlacek Z, Manca A, Kioschis P, Konecki D, Lehrach H, Poustka A (1992). A strategy for the selection of transcribed sequences in the Xq28 region. Hum Mol Genet 1, 235–241

    Article  PubMed  CAS  Google Scholar 

  • Lagercrantz J, Carson E, Larson C, Nordsenskjold M, Gunther W (1995). Isolation and characterization of a novel gene close to the human phosphoinositide-specific phospholipase Cb3 gene on chromosomal region 11q13. Genomics, 31, 380–384

    Article  Google Scholar 

  • Lange E, Borresen A, Chen X, Chessa L, Chiplunkar S, Concannon P, Dandekar S, Gerken S, Lange K, Liang T, McConville C, Polakow J, Porras O, Rotman G, Sanal O, Sheikhavandi S, Shiloh Y, Sobel E, Taylor M, Telatar M, Teraoka S, Tolun A, Udar N, Uhrhammer N, Vanagaite L, Wang Z, Wapelhorst B, Wright J, Yang HM, Yang L, Ziv Y, Gatti RA (1995). Localization of an ataxia-telangiectasia gene to an ~500 kb interval on chromosome 11q23.1: linkage analysis of 176 families by an international consortium. Am J Hum Genet 57, 112–119

    PubMed  CAS  Google Scholar 

  • Loh EY, Elliott JF, Cwirla S, Lanier LL, Davis MM (1989). Polymerase chain reaction with single-sided specificity: analysis of T cell receptor d chain. Science 243, 217–220

    Article  PubMed  CAS  Google Scholar 

  • Nagasawa H, Yamaguchi S, Orri T, Schutgens RBH, Sweetman L, Hashimoto T (1989). Heterogeneity of defects in mitochondrial acetoacetyl-CoA thiolase biosynthesis in fibroblasts from four patients with 3-ketothiolase deficiency. Pediatr Res 26, 145–149

    Article  PubMed  CAS  Google Scholar 

  • Orita M, Suzuki Y, Sellya T, Hayashi K (1989). Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics, 5, 874–879

    Article  PubMed  CAS  Google Scholar 

  • Parimoo S, Pantanjhali SR, Shukla G, Chaplin DD, Weissman SM (1991). cDNA selections: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc Natl Acad Sci USA 88, 9623–9627

    Article  PubMed  CAS  Google Scholar 

  • Pearson WR, Lipman DJ (1988). Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85, 2444–2448

    Article  PubMed  CAS  Google Scholar 

  • Roest PAM, Roberts RG, Sugino S, van Ommen GJB, den Dunnen JT (1993). Protein truncation test (PTT) for rapid detection of translation-terminating mutations. Hum Mol Genet 2, 1719–1721

    Article  PubMed  CAS  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989). Molecular Cloning, A Laboratory Manual 2nd edn. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press)

    Google Scholar 

  • Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NGJ, Taylor AMR, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y(1995). A single ataxia-telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749–1753

    Article  PubMed  CAS  Google Scholar 

  • Shinya E, Shimada T (1994). Identification of two initiator elements in the bidirectional promoter of the human dihydrofolate reductase and mismatch repair protein 1 genes. Nucleic Acids Res 22, 2143–2149

    Article  PubMed  CAS  Google Scholar 

  • White M, Carvalho M, Derse D, O’Brien S, Dean M (1992). Detecting single base substitutions as heteroduplex polymorphisms. Genomics 12, 301–306

    Article  PubMed  CAS  Google Scholar 

  • Worley KC, Wiese BA, Smith RF (1995). BEAUTY: an enhanced BLAST-based search tool that integrates multiple biological information resources into sequence similarity search results. Genome Res 5, 173–184

    Article  PubMed  CAS  Google Scholar 

  • Wright KL, White LC, Kelly A, Beck S, Trowsdale J, Ting J P-Y (1995). Co-ordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. J Exp Med 181, 1459–1471

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The sequence of the gene described here has been submitted to GenBank. Its accession number is U58852.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, X., Yang, L., Udar, N. et al. CAND3: A ubiquitously expressed gene immediately adjacent and in opposite transcriptional orientation to the ATM gene at 1lq23.1. Mammalian Genome 8, 129–133 (1997). https://doi.org/10.1007/s003359900371

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s003359900371

Keywords

Navigation