NEIL1 (nei endonuclease VIII-like 1 (E. coli))
2007-07-01 Masaya Suzuki , Kazuya Shinmura , Haruhiko Sugimura AffiliationDepartment of Pathology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu, Shizuoka 431-3192, Japan
Identity
HGNC
LOCATION
15q24.2
LOCUSID
ALIAS
FPG1,NEI1,hFPG1
FUSION GENES
DNA/RNA
Description
The NEIL1 gene maps on chromosome 15q24.2 spanning 8,179bp. It contains 11 exons, and the orientation is plus strand.
Transcription
The transcript of 1,828bp, expressed in Brain, Liver, Lung, Kidney, Colon, and Stomach. The NEIL1 gene is up-regulated during S-phase.
Proteins
Description
NEIL1 encodes 390 amino acids, theoretical molecular weight is 43684 Da, Formamidopyrimidine-DNA glycosylase N-terminal domain and Formamidopyrimidine-DNA glycosylase H2TH domain.
Localisation
Nucleus, centrosome, and mitotic condensed chromosomes.
Function
(1) Bifunctional DNA glycosylase and apurinic/apyrimidinic (AP) lyase that catalyzes beta- and delta-elimination reactions at the site of damaged base.
(2) Reported substrates: thymine glycol (Tg), 5-hydroxycytosine, 5-hydroxyuracil, 5,6-dihydrouracil, 5,6-dihydrothymine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), 4,6-diamino-5-formamidopyrimidine (FapyA), 5-formyluracil, 5-hydroxymethyluracil, spiroiminodihydantoin (Sp), guanidinohydantoin, (Gh) and 8-hydroxyguanine.
(3) Since NEIL1 catalyzes beta- and delta-elimination reactions, the protein generates DNA strand breaks with 3 phosphate termini. In mammalian cells, this 3 phosphate is removed by polynucleotide kinase, but not by . NEIL1 stably interacts with other BER proteins, DNA polymerase beta and DNA ligase III alpha.
(4) In mammalian BER, DNA glycosylases generate abasic (AP) sites, which are then converted to deoxyribo-5-phosphate (dRP) and excised by a dRP lyase (dRPase) activity of DNA polymerase beta. Since NEIL1 also has dRPase activity, NEIL1 has a role as a backup dRPase in mammalian cells.
(5) NEIL1 has a repair activity for oxidized bases in single-strand DNA and bubble DNA, suggesting a possibility that NEIL1 is preferentially involved in repair of lesions in DNA bubbles generated during transcription and/or replication.
(6) Proteins that associate and stimulate the repair activity of NEIL1: a) The (WRN), a member of RecQ family of DNA helicases, b) , , and as individual proteins and as the 9-1-1 complex.
(7) The major DNA glycosylase for the excision of 8-hydroxyguanine is . In the repair of 8-ydroxyguanine by OGG1, after excising the base lesion, OGG1 remains bound to the resulting AP site and does not turn over efficiently. The APE1, which cleaves the phosphodiester bond 5 to the AP site, displaces the bound OGG1 and thus increases its turnover. NEIL1 stimulates turnover of OGG1 in a fashion similar to that of APE1, and carries out beta/delta- elimination at the AP site.
(8) Although OGG1 has limited activity on 8-hydroxyguanine lesion located in the vicinity of the 3 end of a DNA single-strand break, NEIL1 effectively excises the 3 end proximal 8-hydroxyguanine lesion. NEIL1 also effectively excises 5-hydroxyuracil lesions located in the proximity of the 3-end of a DNA single-strand break. (9) The NEIL1 gene is induced by reactive oxygen species.
(2) Reported substrates: thymine glycol (Tg), 5-hydroxycytosine, 5-hydroxyuracil, 5,6-dihydrouracil, 5,6-dihydrothymine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), 4,6-diamino-5-formamidopyrimidine (FapyA), 5-formyluracil, 5-hydroxymethyluracil, spiroiminodihydantoin (Sp), guanidinohydantoin, (Gh) and 8-hydroxyguanine.
(3) Since NEIL1 catalyzes beta- and delta-elimination reactions, the protein generates DNA strand breaks with 3 phosphate termini. In mammalian cells, this 3 phosphate is removed by polynucleotide kinase, but not by . NEIL1 stably interacts with other BER proteins, DNA polymerase beta and DNA ligase III alpha.
(4) In mammalian BER, DNA glycosylases generate abasic (AP) sites, which are then converted to deoxyribo-5-phosphate (dRP) and excised by a dRP lyase (dRPase) activity of DNA polymerase beta. Since NEIL1 also has dRPase activity, NEIL1 has a role as a backup dRPase in mammalian cells.
(5) NEIL1 has a repair activity for oxidized bases in single-strand DNA and bubble DNA, suggesting a possibility that NEIL1 is preferentially involved in repair of lesions in DNA bubbles generated during transcription and/or replication.
(6) Proteins that associate and stimulate the repair activity of NEIL1: a) The (WRN), a member of RecQ family of DNA helicases, b) , , and as individual proteins and as the 9-1-1 complex.
(7) The major DNA glycosylase for the excision of 8-hydroxyguanine is . In the repair of 8-ydroxyguanine by OGG1, after excising the base lesion, OGG1 remains bound to the resulting AP site and does not turn over efficiently. The APE1, which cleaves the phosphodiester bond 5 to the AP site, displaces the bound OGG1 and thus increases its turnover. NEIL1 stimulates turnover of OGG1 in a fashion similar to that of APE1, and carries out beta/delta- elimination at the AP site.
(8) Although OGG1 has limited activity on 8-hydroxyguanine lesion located in the vicinity of the 3 end of a DNA single-strand break, NEIL1 effectively excises the 3 end proximal 8-hydroxyguanine lesion. NEIL1 also effectively excises 5-hydroxyuracil lesions located in the proximity of the 3-end of a DNA single-strand break. (9) The NEIL1 gene is induced by reactive oxygen species.
Homology
Homo sapiens: (NP_659480, 20.1%), (NP_060718, 15.0%) using the CLUSTALW software.
Implicated in
Entity name
Gastric cancer
Note
The following is the abstract of the paper by Shinmura K. et al. (Carcinogenesis, 2004). Oxidized DNA base lesions, such as thymine glycol (Tg) and 8-hydroxyguanine, are often toxic and mutagenic and have been implicated in carcinogenesis. To clarify whether NEIL1 protein, which exhibits excision repair activity towards such base lesions, is involved in gastric carcinogenesis, we examined 71 primary gastric cancers from Japanese patients and four gastric cancer cell lines for mutations and genetic polymorphisms of the NEIL1 gene. We also examined 20 blood samples from Chinese patients for NEIL1 genetic polymorphisms. Three mutations (c.82_84delGAG:p.Glu28del, c.936G > A and c.1000A > G:p.Arg334Gly) and two genetic polymorphisms were identified. When the excision repair activity towards double-stranded oligonucleotide containing a Tg:A base pair was compared among six types of recombinant NEIL1 proteins, p.Glu28del-type NEIL1, found in a primary case, was found to exhibit an extremely low activity level. Moreover, c.936G > A, located in the last nucleotide of exon 10 and detected in the KATO-III cell line, was shown to be associated with a splicing abnormality using an in vivo splicing assay. An immunofluorescence analysis showed that the wild-type NEIL1 protein, but not the truncated protein encoded by the abnormal transcript arising from the c.936G > A mutation, was localized in the nucleus, suggesting that the truncated protein is unlikely to be capable of repairing nuclear DNA. An expression analysis revealed that NEIL1 mRNA expression was reduced in six of 13 (46%) primary gastric cancer specimens that were examined. These results suggest that low NEIL1 activities arising from mutations and reduced expression may be involved in the pathogenesis in a subset of gastric cancers.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17101234 | 2007 | Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress. | Akbari M et al |
| 15907775 | 2005 | Action of human endonucleases III and VIII upon DNA-containing tandem dihydrouracil. | Ali MM et al |
| 15159582 | 2004 | Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damage. | Bandaru V et al |
| 12509226 | 2002 | A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII. | Bandaru V et al |
| 17627905 | 2007 | Human endonuclease VIII-like (NEIL) proteins in the giant DNA Mimivirus. | Bandaru V et al |
| 17611195 | 2007 | The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1. | Das A et al |
| 16118226 | 2005 | Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species. | Das A et al |
| 16978929 | 2007 | Major oxidative products of cytosine are substrates for the nucleotide incision repair pathway. | Daviet S et al |
| 14522990 | 2003 | Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. | Dou H et al |
| 15232006 | 2004 | The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity. | Doublié S et al |
| 16920106 | 2006 | Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins. | Grin IR et al |
| 17395641 | 2007 | The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. | Guan X et al |
| 15533836 | 2005 | Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2. | Hailer MK et al |
| 11904416 | 2002 | Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. | Hazra TK et al |
| 12097317 | 2002 | Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions. | Hazra TK et al |
| 16793361 | 2006 | Purification and characterization of NEIL1 and NEIL2, members of a distinct family of mammalian DNA glycosylases for repair of oxidized bases. | Hazra TK et al |
| 17556049 | 2007 | Human NEIL1 localizes with the centrosomes and condensed chromosomes during mitosis. | Hildrestrand GA et al |
| 16221681 | 2005 | Repair of formamidopyrimidines in DNA involves different glycosylases: role of the OGG1, NTH1, and NEIL1 enzymes. | Hu J et al |
| 15038771 | 2004 | Expression of the oxidative base excision repair enzymes is not induced in TK6 human lymphoblastoid cells after low doses of ionizing radiation. | Inoue M et al |
| 15595846 | 2004 | Mouse NEIL1 protein is specific for excision of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine from oxidatively damaged DNA. | Jaruga P et al |
| 17432829 | 2007 | Lesion specificity in the base excision repair enzyme hNeil1: modeling and dynamics studies. | Jia L et al |
| 14734554 | 2004 | Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions. | Katafuchi A et al |
| 12600212 | 2003 | Cross-linking of 2-deoxyribonolactone and its beta-elimination product by base excision repair enzymes. | Kroeger KM et al |
| 14726482 | 2004 | Stereoselective excision of thymine glycol from oxidatively damaged DNA. | Miller H et al |
| 15350146 | 2004 | Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases. | Mokkapati SK et al |
| 12433996 | 2002 | Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA. | Morland I et al |
| 16446124 | 2006 | Repair of thymine glycol by hNth1 and hNeil1 is modulated by base pairing and cis-trans epimerization. | Ocampo-Hafalla MT et al |
| 17348689 | 2007 | NEIL1 is the major DNA glycosylase that processes 5-hydroxyuracil in the proximity of a DNA single-strand break. | Parsons JL et al |
| 12713815 | 2003 | The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. | Rosenquist TA et al |
| 17389588 | 2007 | Human polymorphic variants of the NEIL1 DNA glycosylase. | Roy LM et al |
| 16545110 | 2006 | Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas. | Sarebø M et al |
| 15319300 | 2004 | Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer. | Shinmura K et al |
| 12200441 | 2002 | A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue. | Takao M et al |
| 16446448 | 2006 | The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. | Vartanian V et al |
| 15260972 | 2004 | AP endonuclease-independent DNA base excision repair in human cells. | Wiederhold L et al |
| 15533839 | 2005 | DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells. | Zhang QM et al |
Other Information
Locus ID:
NCBI: 79661
MIM: 608844
HGNC: 18448
Ensembl: ENSG00000140398
Variants:
dbSNP: 79661
ClinVar: 79661
TCGA: ENSG00000140398
COSMIC: NEIL1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA128406956 | fluorouracil | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA164713176 | Platinum compounds | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA166122986 | radiotherapy | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA445742 | Stomach Neoplasms | Disease | VariantAnnotation | not associated | PD | 28796378 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38795603 | 2024 | Functional characterization of single nucleotide polymorphic variants of DNA repair enzyme NEIL1 in South Asian populations. | 0 |
| 38795603 | 2024 | Functional characterization of single nucleotide polymorphic variants of DNA repair enzyme NEIL1 in South Asian populations. | 0 |
| 37517321 | 2023 | Functional analyses of single nucleotide polymorphic variants of the DNA glycosylase NEIL1 in sub-Saharan African populations. | 2 |
| 37517321 | 2023 | Functional analyses of single nucleotide polymorphic variants of the DNA glycosylase NEIL1 in sub-Saharan African populations. | 2 |
| 35190641 | 2022 | p53-NEIL1 co-abnormalities induce genomic instability and promote synthetic lethality with Chk1 inhibition in multiple myeloma having concomitant 17p13(del) and 1q21(gain). | 4 |
| 35917336 | 2022 | NEIL1 Recoding due to RNA Editing Impacts Lesion-Specific Recognition and Excision. | 4 |
| 35190641 | 2022 | p53-NEIL1 co-abnormalities induce genomic instability and promote synthetic lethality with Chk1 inhibition in multiple myeloma having concomitant 17p13(del) and 1q21(gain). | 4 |
| 35917336 | 2022 | NEIL1 Recoding due to RNA Editing Impacts Lesion-Specific Recognition and Excision. | 4 |
| 33300026 | 2021 | Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin. | 18 |
| 33498912 | 2021 | Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter. | 4 |
| 33595290 | 2021 | DNA Sequence Modulates the Efficiency of NEIL1-Catalyzed Excision of the Aflatoxin B(1)-Induced Formamidopyrimidine Guanine Adduct. | 8 |
| 33925271 | 2021 | NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487. | 6 |
| 33929180 | 2021 | RNA Editing of the Human DNA Glycosylase NEIL1 Alters Its Removal of 5-Hydroxyuracil Lesions in DNA. | 3 |
| 34105905 | 2021 | Genetic variations in DNA repair gene NEIL1 associated with radiation pneumonitis risk in lung cancer patients. | 1 |
| 34226550 | 2021 | DNA repair glycosylase hNEIL1 triages damaged bases via competing interaction modes. | 5 |
Citation
Masaya Suzuki ; Kazuya Shinmura ; Haruhiko Sugimura
NEIL1 (nei endonuclease VIII-like 1 (E. coli))
Atlas Genet Cytogenet Oncol Haematol. 2007-07-01
Online version: http://atlasgeneticsoncology.org/gene/41519/neil1
