title: 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.
abstract: Genomic cloning and sequencing of a human homologue (the gene name, endonuclease III-like 1; gene symbol, NTHL1 or NTH1) for Escherichia coli endonuclease III, that is involved in pyrimidine base excision repair, were performed. The sequence covered the entire NTHL1 gene consisting of six exons and five introns spanning 8kb with 5' flanking (8kb) and 3' flanking (3.8kb) regions. Southern blot analysis suggested that the NTHL1 gene exists as a single copy in a haploid genome. The sequenced 5' flanking region lacks typical TATA and CAAT boxes, but contains a CpG island having putative binding sites for several transcription factors such as Ets1 and Sp1. The NTHL1 gene lies immediately adjacent to the tuberous sclerosis 2 (TSC2) gene on chromosome 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 experiments. The northern hybridization experiment suggested that both genes are expressed in all tissues, but at different levels. Downstream of the NTHL1 gene, the gene for the regulatory factor 2 (SLC9A3R2/E3KARP; also called OCTS2, TKA-1 and SIP-1) of the solute carrier family 9 (sodium/hydrogen exchanger), isoform A3, lies in a 3'-to-3' orientation. This paper demonstrates for the first time the spatial relationship of these three genes (TSC2, NTHL1 and SLC9A3R2) at the nucleotide level, and the presence of multiple transcription initiation sites of the NTHL1 and TSC2 genes.
authors.affiliation: Department of Molecular Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama 700-8558, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: A H
authors.initials: AH
authors.lastname: Sarker
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Tsutsui
authors.forename: T
authors.initials: T
authors.lastname: Shohmori
authors.forename: S
authors.initials: S
authors.lastname: Seki
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D029968:Escherichia coli Proteins; D015870:Gene Expression; D005798:Genes, Bacterial; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D017931:DNA Primers; D029968:Escherichia coli Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D017923:Sodium-Hydrogen Exchangers; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C093376:sodium-hydrogen exchanger regulatory factor; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; C468347:NTHL1 protein, human