Genomic structure and chromosomal localization of the human deoxycytidine kinase gene

Journal Article · Fri Jan 15 04:00:00 EST 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.2.431· OSTI ID:6448569

Song, J J; Walker, S; Gribbin, T ^[1]; Chen, E ^[2]; Johnson, E E; Spychala, J; Mitchell, B S ^[3]

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1. Univ. of Michigan Medical Center, Ann Arbor (United States)
2. Univ. of Michigan Medical Center, Ann Arbor (United States) Univ. of North Carolina, Chapel Hill (United States)
3. Univ. of North Carolina, Chapel Hill (United States)

Deoxycytidine kinase (NTP:deoxycytidine 5[prime]-phosphotransferase, EC 2.7.1.74) is an enzyme that catalyzes phosphorylation of deoxyribonucleosides and a number of nucleoside analogs that are important in antiviral and cancer chemotherapy. Deficiency of this enzyme activity is associated with resistance to these agents, whereas increased enzyme activity is associated with increased activation of such compounds to cytotoxic nucleoside triphosphate derivatives. To characterize the regulation of expression of this gene, we have isolated genomic clones encompassing its entire coding and 5[prime] flanking regions and delinated all the exon/intron boundaries. The gene extends over more than 34 kilobases on chromosome 4 and the coding region is composed of 7 exons ranging in size from 90 to 1544 base pairs (bp). The 5[prime] flanking region is highly G+C-rich and contains four regions that are potential Sp1 binding sites. A 697-bp fragment encompassing 386 bp of 5[prime] upstream region, the 250-bp first exon, and 61 bp of the first intron was demonstrated to promote chloramphenicol acetyltransferase activity in a T-lymphoblast cell line and to have >6-fold greater activity in a Jurkat T-lymphoblast than in a Raji B-lymphoblast cell line. Our data suggest that these 5[prime] sequences may contain elements that are important for the tissue-specific differences in deoxycytidine kinase expression. 32 refs., 4 figs., 2 tabs.

• OSTI ID: 6448569
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 90:2; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AZINES
CATABOLISM
CHEMICAL REACTIONS
CHEMOTHERAPY
CHLORAMPHENICOL
CHROMOSOMES
DEOXYCYTIDINE
DNA
DRUGS
ENZYME ACTIVITY
ENZYMES
GENES
HETEROCYCLIC COMPOUNDS
HUMAN CHROMOSOMES
MAPPING
METABOLISM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
PYRIMIDINES
RIBOSIDES
THERAPY
TRANSFERASES