NEIL1 (nei endonuclease VIII-like 1 (E. coli))

Identity

Other names	FLJ22402
	FPG1
	hFPG1
	NEH1
	NEI1
HGNC	NEIL1
Location	15q24.2

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.

Protein

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.
Homology	Homo sapiens: (NP_659480, 20.1%), (NP_060718, 15.0%) using the CLUSTALW software.

Implicated in

Entity	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.

External links

	Nomenclature
HGNC	NEIL1   18448
Entrez_Gene	NEIL1  79661  nei endonuclease VIII-like 1 (E. coli)
	Cards
Atlas	NEIL1ID41519ch15q24
GeneCards	NEIL1
Ensembl	NEIL1 [Search_View]   ENSG00000140398 [Gene_View]
Genatlas	NEIL1
GeneLynx	NEIL1
eGenome	NEIL1
euGene	79661
	Genomic and cartography
GoldenPath	NEIL1  -  15q24.2   chr15:73426463-73434641 +  15q33.33   [Description]    (hg18-Mar_2006)
Ensembl	NEIL1 - 15q33.33 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	NEIL1
	Gene and transcription
Genbank	AB079068 [ ENTREZ ]
Genbank	AK026055 [ ENTREZ ]
Genbank	AK026216 [ ENTREZ ]
Genbank	AK097008 [ ENTREZ ]
Genbank	AK128372 [ ENTREZ ]
RefSeq	NM_024608 [ SRS ]    NM_024608 [ ENTREZ ]
RefSeq	AC_000058 [ SRS ]    AC_000058 [ ENTREZ ]
RefSeq	AC_000147 [ SRS ]    AC_000147 [ ENTREZ ]
RefSeq	NC_000015 [ SRS ]    NC_000015 [ ENTREZ ]
RefSeq	NT_010194 [ SRS ]    NT_010194 [ ENTREZ ]
RefSeq	NW_001838219 [ SRS ]    NW_001838219 [ ENTREZ ]
RefSeq	NW_925907 [ SRS ]    NW_925907 [ ENTREZ ]
AceView	NEIL1 AceView - NCBI
Unigene	Hs.512732 [ SRS ]    Hs.512732 [ NCBI ]     HS512732 [ spliceNest ]
Fast-db	8481 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q96FI4 [ SRS]    Q96FI4 [ EXPASY ]     Q96FI4 [ INTERPRO ]     Q96FI4 [ UNIPROT ]
Prosite	PS51068 FPG_CAT [ SRS ]    PS51068 FPG_CAT [ Expasy ]
Interpro	IPR015886 DNA_glyclase/AP_lyase_DNA-bd [ SRS ]    IPR015886 DNA_glyclase/AP_lyase_DNA-bd [ EBI ]
Interpro	IPR015887 DNA_glyclase_Znf_dom_DNA_BS [ SRS ]    IPR015887 DNA_glyclase_Znf_dom_DNA_BS [ EBI ]
Interpro	IPR012319 DNA_glycosylase/AP_lyase_cat [ SRS ]    IPR012319 DNA_glycosylase/AP_lyase_cat [ EBI ]
Interpro	IPR015371 Endonuclease-VIII_DNA_bd [ SRS ]    IPR015371 Endonuclease-VIII_DNA_bd [ EBI ]
CluSTr	Q96FI4
Pfam	PF01149 Fapy_DNA_glyco [ SRS ]    PF01149 Fapy_DNA_glyco [ Sanger ]    pfam01149 [ NCBI-CDD ]
Pfam	PF06831 H2TH [ SRS ]    PF06831 H2TH [ Sanger ]    pfam06831 [ NCBI-CDD ]
Pfam	PF09292 Neil1-DNA_bind [ SRS ]    PF09292 Neil1-DNA_bind [ Sanger ]    pfam09292 [ NCBI-CDD ]
Prodom	PD003680 Fapy_DNA_glyco[INRA-Toulouse]
Prodom	Q96FI4 NEIL1_HUMAN [ Domain structure ]   Q96FI4 NEIL1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	Q96FI4
PDB	1TDH [ SRS ]    1TDH [ PdbSum ],   1TDH [ IMB ]   1TDH [ RSDB ]
HPRD	12314
	Protein Interaction databases
DIP	Q96FI4
IntAct	Q96FI4
	Polymorphism : SNP, mutations, diseases
OMIM	608844    [ map ]
GENECLINICS	608844
SNP	NEIL1 [dbSNP-NCBI]
SNP	NM_024608 [SNP-NCI]
SNP	NEIL1 [GeneSNPs - Utah]  NEIL1] [HGBASE - SRS]
HAPMAP	NEIL1 [HAPMAP]
COSMIC	NEIL1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	NEIL1
	General knowledge
Family Browser	NEIL1 [UCSC Family Browser]
SOURCE	NM_024608
SMD	Hs.512732
SAGE	Hs.512732
Enzyme	3.2.2.- [ Enzyme-Expasy ]   3.2.2.- [ Enzyme-SRS ]   3.2.2.- [ IntEnz-EBI ]   3.2.2.- [ BRENDA ]   3.2.2.- [ KEGG ]   3.2.2.- [ WIT ]
GO	damaged DNA binding [Amigo]  damaged DNA binding
GO	DNA-(apurinic or apyrimidinic site) lyase activity [Amigo]  DNA-(apurinic or apyrimidinic site) lyase activity
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	base-excision repair [Amigo]  base-excision repair
GO	nucleotide-excision repair [Amigo]  nucleotide-excision repair
GO	response to oxidative stress [Amigo]  response to oxidative stress
GO	protein C-terminus binding [Amigo]  protein C-terminus binding
GO	metabolic process [Amigo]  metabolic process
GO	zinc ion binding [Amigo]  zinc ion binding
GO	hydrolase activity, hydrolyzing N-glycosyl compounds [Amigo]  hydrolase activity, hydrolyzing N-glycosyl compounds
GO	lyase activity [Amigo]  lyase activity
GO	negative regulation of nuclease activity [Amigo]  negative regulation of nuclease activity
PubGene	NEIL1
TreeFam	NEIL1
CTD	79661 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	NEIL1 Related clones (RZPD - Berlin)
	PubMed
PubMed	30 Pubmed reference(s) in LocusLink

Bibliography

A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII.

Bandaru V, Sunkara S, Wallace SS, Bond JP

DNA repair. 2002 ; 1 (7) : 517-529.

PMID 12509226

Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA.

Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, Jaruga P, Dizdaroglu M, Mitra S

Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (6) : 3523-3528.

PMID 11904416

Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions.

Hazra TK, Kow YW, Hatahet Z, Imhoff B, Boldogh I, Mokkapati SK, Mitra S, Izumi T

The Journal of biological chemistry. 2002 ; 277 (34) : 30417-30420.

PMID 12097317

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, Rolseth V, Luna L, Rognes T, Bjˆ½rˆ€s M, Seeberg E

Nucleic acids research. 2002 ; 30 (22) : 4926-4936.

PMID 12433996

A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue.

Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A

The Journal of biological chemistry. 2002 ; 277 (44) : 42205-42213.

PMID 12200441

Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2.

Dou H, Mitra S, Hazra TK

The Journal of biological chemistry. 2003 ; 278 (50) : 49679-49684.

PMID 14522990

Cross-linking of 2-deoxyribonolactone and its beta-elimination product by base excision repair enzymes.

Kroeger KM, Hashimoto M, Kow YW, Greenberg MM

Biochemistry. 2003 ; 42 (8) : 2449-2455.

PMID 12600212

The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death.

Rosenquist TA, Zaika E, Fernandes AS, Zharkov DO, Miller H, Grollman AP

DNA repair. 2003 ; 2 (5) : 581-591.

PMID 12713815

Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damage.

Bandaru V, Cooper W, Wallace SS, Doubliˆ© S

Acta crystallographica. Section D, Biological crystallography. 2004 ; 60 (Pt 6) : 1142-1144.

PMID 15159582

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity.

Doubliˆ© S, Bandaru V, Bond JP, Wallace SS

Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (28) : 10284-10289.

PMID 15232006

Expression of the oxidative base excision repair enzymes is not induced in TK6 human lymphoblastoid cells after low doses of ionizing radiation.

Inoue M, Shen GP, Chaudhry MA, Galick H, Blaisdell JO, Wallace SS

Radiation research. 2004 ; 161 (4) : 409-417.

PMID 15038771

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, Birincioglu M, Rosenquist TA, Dizdaroglu M

Biochemistry. 2004 ; 43 (50) : 15909-15914.

PMID 15595846

Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions.

Katafuchi A, Nakano T, Masaoka A, Terato H, Iwai S, Hanaoka F, Ide H

The Journal of biological chemistry. 2004 ; 279 (14) : 14464-14471.

PMID 14734554

Stereoselective excision of thymine glycol from oxidatively damaged DNA.

Miller H, Fernandes AS, Zaika E, McTigue MM, Torres MC, Wente M, Iden CR, Grollman AP

Nucleic acids research. 2004 ; 32 (1) : 338-345.

PMID 14726482

Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases.

Mokkapati SK, Wiederhold L, Hazra TK, Mitra S

Biochemistry. 2004 ; 43 (36) : 11596-11604.

PMID 15350146

Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer.

Shinmura K, Tao H, Goto M, Igarashi H, Taniguchi T, Maekawa M, Takezaki T, Sugimura H

Carcinogenesis. 2004 ; 25 (12) : 2311-2317.

PMID 15319300

AP endonuclease-independent DNA base excision repair in human cells.

Wiederhold L, Leppard JB, Kedar P, Karimi-Busheri F, Rasouli-Nia A, Weinfeld M, Tomkinson AE, Izumi T, Prasad R, Wilson SH, Mitra S, Hazra TK

Molecular cell. 2004 ; 15 (2) : 209-220.

PMID 15260972

Action of human endonucleases III and VIII upon DNA-containing tandem dihydrouracil.

Ali MM, Hazra TK, Hong D, Kow YW

DNA repair. 2005 ; 4 (6) : 679-686.

PMID 15907775

Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species.

Das A, Hazra TK, Boldogh I, Mitra S, Bhakat KK

The Journal of biological chemistry. 2005 ; 280 (42) : 35272-35280.

PMID 16118226

Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2.

Hailer MK, Slade PG, Martin BD, Rosenquist TA, Sugden KD

DNA repair. 2005 ; 4 (1) : 41-50.

PMID 15533836

Repair of formamidopyrimidines in DNA involves different glycosylases: role of the OGG1, NTH1, and NEIL1 enzymes.

Hu J, de Souza-Pinto NC, Haraguchi K, Hogue BA, Jaruga P, Greenberg MM, Dizdaroglu M, Bohr VA

The Journal of biological chemistry. 2005 ; 280 (49) : 40544-40551.

PMID 16221681

NEIL1 excises 3' end proximal oxidative DNA lesions resistant to cleavage by NTH1 and OGG1.

Parsons JL, Zharkov DO, Dianov GL

Nucleic acids research. 2005 ; 33 (15) : 4849-4856.

PMID 16129732

DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells.

Zhang QM, Yonekura S, Takao M, Yasui A, Sugiyama H, Yonei S

DNA repair. 2005 ; 4 (1) : 71-79.

PMID 15533839

Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas.

Sarebˆ½ M, Skjelbred CF, Breistein R, Lothe IM, Hagen PC, Bock G, Hansteen IL, Kure EH

BMC cancer. 2006 ; 6 : page 71.

PMID 16545110

Deoxyribophosphate lyase activity of mammalian endonuclease VIII-like proteins.

Grin IR, Khodyreva SN, Nevinsky GA, Zharkov DO

FEBS letters. 2006 ; 580 (20) : 4916-4922.

PMID 16920106

Purification and characterization of NEIL1 and NEIL2, members of a distinct family of mammalian DNA glycosylases for repair of oxidized bases.

Hazra TK, Mitra S

Methods in enzymology. 2006 ; 408 : 33-48.

PMID 16793361

Repair of thymine glycol by hNth1 and hNeil1 is modulated by base pairing and cis-trans epimerization.

Ocampo-Hafalla MT, Altamirano A, Basu AK, Chan MK, Ocampo JE, Cummings A Jr, Boorstein RJ, Cunningham RP, Teebor GW

DNA repair. 2006 ; 5 (4) : 444-454.

PMID 16446124

The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase.

Vartanian V, Lowell B, Minko IG, Wood TG, Ceci JD, George S, Ballinger SW, Corless CL, McCullough AK, Lloyd RS

Proceedings of the National Academy of Sciences of the United States of America. 2006 ; 103 (6) : 1864-1869.

PMID 16446448

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, Otterlei M, Peˆ±a-Diaz J, Krokan HE

Neuroscience. 2007 ; 145 (4) : 1201-1212.

PMID 17101234

Human endonuclease VIII-like (NEIL) proteins in the giant DNA Mimivirus.

Bandaru V, Zhao X, Newton MR, Burrows CJ, Wallace SS

DNA repair. 2007 ; 6 (11) : 1629-1641.

PMID 17627905

Major oxidative products of cytosine are substrates for the nucleotide incision repair pathway.

Daviet S, Couvˆ©-Privat S, Gros L, Shinozuka K, Ide H, Saparbaev M, Ishchenko AA

DNA repair. 2007 ; 6 (1) : 8-18.

PMID 16978929

The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1.

Das A, Boldogh I, Lee JW, Harrigan JA, Hegde ML, Piotrowski J, de Souza Pinto N, Ramos W, Greenberg MM, Hazra TK, Mitra S, Bohr VA

The Journal of biological chemistry. 2007 ; 282 (36) : 26591-26602.

PMID 17611195

The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase.

Guan X, Bai H, Shi G, Theriot CA, Hazra TK, Mitra S, Lu AL

Nucleic acids research. 2007 ; 35 (8) : 2463-2472.

PMID 17395641

Human NEIL1 localizes with the centrosomes and condensed chromosomes during mitosis.

Hildrestrand GA, Rolseth V, Bjˆ½rˆ€s M, Luna L

DNA repair. 2007 ; 6 (10) : 1425-1433.

PMID 17556049

Lesion specificity in the base excision repair enzyme hNeil1: modeling and dynamics studies.

Jia L, Shafirovich V, Geacintov NE, Broyde S

Biochemistry. 2007 ; 46 (18) : 5305-5314.

PMID 17432829

NEIL1 is the major DNA glycosylase that processes 5-hydroxyuracil in the proximity of a DNA single-strand break.

Parsons JL, Kavli B, Slupphaug G, Dianov GL

Biochemistry. 2007 ; 46 (13) : 4158-4163.

PMID 17348689

Human polymorphic variants of the NEIL1 DNA glycosylase.

Roy LM, Jaruga P, Wood TG, McCullough AK, Dizdaroglu M, Lloyd RS

The Journal of biological chemistry. 2007 ; 282 (21) : 15790-15798.

PMID 17389588

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Contributor(s)

Written	07-2007	Masaya Suzuki, Kazuya Shinmura, Haruhiko Sugimura
		Department of Pathology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu, Shizuoka 431-3192, Japan

Citation

This paper should be referenced as such :

Suzuki M, Shinmura K, Sugimura H . NEIL1 (nei endonuclease VIII-like 1 (E. coli)). Atlas Genet Cytogenet Oncol Haematol. July 2007 . URL : http://AtlasGeneticsOncology.org/Genes/NEIL1ID41519ch15q24.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:15:47 2008