Disease relevance of NEIL1

• The structure of NEIL1 exhibits the same overall fold as E. coli Nei, albeit with an unexpected twist [1].
• An expression analysis revealed that NEIL1 mRNA expression was reduced in six of 13 (46%) primary gastric cancer specimens that were examined [2].
• In the absence of exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/-) mice develop severe obesity, dyslipidemia, and fatty liver disease and also have a tendency to develop hyperinsulinemia [3].
• Dr. Neil Goldsworthy had a profound effect on the development of dental research in the biological sciences in Australia, including measures for the prevention of dental caries [4].
• Clinical experiments undertaken at the Land Headquarters Medical Research Unit of the Australian Army in Cairns, under the direction of Neil Hamilton Fairley, demonstrated that atebrin was able to provide complete protection against vivax and falciparum malaria [5].

Psychiatry related information on NEIL1

• Internal medicine's identity crisis. Interview by Neil Chesanow [6].
• Neil Armstrong, director of the Coronary Prevention in Children Project, argues for a comprehensive programme for promoting children's physical activity [7].

High impact information on NEIL1

• The complex of NEIL1, pol beta, and DNA ligase IIIalpha together with PNK suggests coordination of NEIL1-initiated repair [8].
• Here, Neil Greenspan and Laurence Cooper review evidence for these effects, and explore implications of the conclusion that effective specificity in multivalent interactions is not completely determined by the degree of complementarity between epitopes and paratopes [9].
• In humans, this combination of clinical manifestations, including hypertension, is known as the metabolic syndrome and is estimated to affect >40 million people in the United States. Additionally, mitochondrial DNA from neil1-/- mice show increased levels of steady-state DNA damage and deletions relative to wild-type controls [3].
• Sequence alignments had predicted that NEIL1 would lack a zinc finger, and it was therefore expected to use a different DNA-binding motif instead [1].
• This "zincless finger" appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme [1].

Chemical compound and disease context of NEIL1

• Recently, NEIL1, a human homolog of Escherichia coli DNA glycosylase endonuclease VIII, has been identified and shown to exhibit broad substrate specificity for a variety of types of pyrimidine-base damage [10].

Biological context of NEIL1

• These results suggest that NEIL1 is a back-up glycosylase for NTH1 with unique substrate specificity and tissue-specific expression [11].
• However, unlike NEIL1, its expression was independent of the cell cycle stage in fibroblasts, and its highest expression was observed in the testes and skeletal muscle [12].
• NEIL2 is similar to NEIL1 in having N-terminal Pro as the active site [12].
• In spite of their limited sequence homology, NEIL1 and NEIL2 interact with the same domains of Pol beta and Lig IIIalpha [13].
• The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death [14].

Anatomical context of NEIL1

• We have also used RNA interference technology to establish embryonic stem cell lines deficient in Neil1 protein and showed them to be sensitive to low levels of gamma-irradiation [14].
• Tissue expression of this mouse Nei-like (designated as Neil1) gene is ubiquitous but much lower than that of mNth1 except in heart, spleen, and skeletal muscle [11].
• 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 [2].
• A similar oxidative stress-induced increase in human NEIL1 (hNEIL1) promoter-dependent luciferase expression in HCT116 cells indicates that reactive oxygen species activates NEIL1 transcription [15].
• Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C [16].

Associations of NEIL1 with chemical compounds

• In addition, the mouse NEIL1 has a unique DNA glycosylase/lyase activity toward mismatched uracil and thymine, especially in U:C and T:C mismatches [11].
• Recombinant NEIL1 can remove thymine glycol and 5-hydroxyuracil in double- and single-stranded DNA much more efficiently than 8-oxoguanine and can nick the strand by an associated (beta-delta) apurinic/apyrimidinic lyase activity [11].
• Exposure of HCT116 human colon carcinoma cells to reactive oxygen species, generated by glucose oxidase (GO), enhanced the levels of NEIL1 mRNA and polypeptide by 2-4-fold by 6 h after GO treatment [15].
• NEIL1 Is the Major DNA Glycosylase that Processes 5-Hydroxyuracil in the Proximity of a DNA Single-Strand Break [17].
• Two of the enzymes, FPG and NEIL1 known to cleave normal abasic sites (1) by effecting beta,delta-elimination form cross-links to the butenolide lesion (4) [18].

Physical interactions of NEIL1

• NEIL1 interacts with PCNA via a domain that is located in a region near the C terminus, dispensable for base excision activity [19].

Other interactions of NEIL1

• We showed earlier that the 3' phosphate generated by NEIL1 is efficiently removed by polynucleotide kinase (PNK) and not APE1 [13].
• Three human genes, designated NEIL1, NEIL2 and NEIL3, encode proteins that contain sequence homologies to Nei and Fpg [14].
• Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases [20].
• Subsequently, we found that although both SMUG1 and NEIL1 are able to excise 5-OHU lesions located in the proximity of the 3'-end of a DNA SSB, NEIL1 is more efficient in the repair of these DNA lesions [17].
• The present study shows that NEIL1 could also participate in strand displacement repair synthesis (long patch repair (LP-BER)) mediated by FEN-1 and stimulated by PCNA [21].

Analytical, diagnostic and therapeutic context of NEIL1

• 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 [2].
• Radiologic considerations of intensive care in the premature infant. Annual oration in honor of William Henry Neil, M.D., 1924-1972 [22].
• 'Nurse of the Year' develops home traction for infants. Interview by Neil and Joanna Gilbride [23].
• Summary of immunohistologic dissection of the human kidney using monoclonal antibodies (by Neil H. Bander, MD, Carlos Cordon-Cardo, MD, PhD, Connie L. Finstad, PhD, Willet F. Whitmore, Jr, MD, E. Darracott Vaughan, Jr, MD, Herbert F. Oettgen, MD, Myron Melamed, MD, and Lloyd J. Old, MD). 1985 [24].
• In June 1943 arrangements were made to carry out experiments on malaria suppressive drugs on human volunteers in Cairns, in north Queensland, under the direction of Brigadier Neil Hamilton Fairley; early in 1944 the Land Headquarters Medical Research Unit was established to continue this work [25].

References