D. Shiokawa et S. Tanuma, Isolation and characterization of the DLAD/Dlad genes, which lie head-to-head with the genes for urate oxidase, BIOC BIOP R, 288(5), 2001, pp. 1119-1128
Citations number
30
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
We previously found that a novel DNA endonuclease named DLAD (DNase II-Like
Acid DNase) is specifically expressed in murine liver. Here, we describe t
he isolation and characterization of the human DLAD and mouse Mad genes. Bo
th DLAD and Mad consist of 6 exons. DLAD encodes a 361 amino acid protein s
haring 34.6% amino acid identity with human DNase II. Although a recombinan
t protein for the putative human DLAD has a divalent cation-independent aci
d DNase activity, expression of the MAD mRNA containing the entire open rea
ding frame was not detected in any human tissues tested, except for lung, i
n which a short 1.1 kb transcript lacking the first two exons is expressed.
Interestingly, sequence analysis of Mad showed that the 1st exon of the ur
ate oxidase gene, Uox, is located on the opposite strand in its 5'-flanking
region. The head-to-head organization of DLAD and UOX is conserved in the
human genomic sequence. Promoter analysis revealed that the intergenic regi
on between Mad and Uox has promoter activity for both the Mad and Uox direc
tions, however, the corresponding human genomic fragment has promoter activ
ity only for DLAD. It is known that murine Uox is expressed only in the liv
er, whereas human UOX has been inactivated as a pseudogene. On the basis of
these results, the expression of DLAD/Dlad and UOX/Uox is suggested to be
coordinated by a common regulatory mechanism(s), and the balance between th
e two enzymes is thought to be important for maintaining the purine nucleot
ide pool in the liver. (C) 2001 Academic Press.