Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes

Genomic cloning and sequencing of a human homologue (the gene name, endonuc lease III-like 1; gene symbol, NTHL1 or NTH1) for Escherichia coli endonucl ease III, that is involved in pyrimidine base excision repair, were perform ed. The sequence covered the entire NTHL1 gene consisting of six exons and five introns spanning 8 kb with 5' Banking (8 kb) and 3' flanking (3.8 kb) regions. Southern blot analysis suggested that the NTHL1 gene exists as a s ingle copy in a haploid genome. The sequenced 5' flanking region lacks typi cal TATA and CAAT boxes, but contains a CpG island having putative binding sites for several transcription factors such as Ets1 and Sp1. The NTHL1 gen e lies immediately adjacent to the tuberous sclerosis 2 (TSC2) gene on chro mosome 16p13.3 in a 5'-to-5' orientation. Transcription initiation sites of both NTHL1 and TSC2 genes were suggested to be multiple by 5' RACE experim ents. The northern hybridization experiment suggested that both genes are e xpressed in all tissues, but at different levels. Downstream of the NTHL1 g ene, the gene for the regulatory factor 2 (SLC9A3R2/E3KARP; also called OCT S2, TKA-1 and SIP-1) of the solute carrier family 9 (sodium/hydrogen exchan ger), isoform A3, lies in a 3'-to-3' orientation. This paper demonstrates f or the first time the spatial relationship of these three genes (TSC2, NTHL 1 and SLC9A3R2) at the nucleotide level, and the presence of multiple trans cription initiation sites of the NTHL1 and TSC2 genes. (C) 1998 Elsevier Sc ience B.V. All rights reserved.