Disease relevance of NEIL2

• The recently identified human NEIL2 (Nei-like-2) protein, a DNA glycosylase/AP lyase specific for oxidatively damaged bases, shares structural features and reaction mechanism with the Escherichia coli DNA glycosylases, Nei and Fpg [1].
• Polymorphisms of the NEIL2 gene may be markers for risk and progression of SCCOOP, particularly in patients with oropharyngeal cancer [2].

High impact information on NEIL2

• In human cells, oxidative pyrimidine lesions are restored by the base excision repair pathway initiated by homologues of Endo III (hNTH1) and Endo VIII (hNEIL1 and hNEIL2) [3].
• We thereby conclude that the zinc finger motif in NEIL2 is essential for its structural integrity and enzyme activity [1].
• Amino acid sequence analysis of NEIL2 suggested it to have a zinc finger-like Nei/Fpg [1].
• However, the Cys-X2-His-X16-Cys-X2-Cys (CHCC) motif present near the C terminus of NEIL2 is distinct from the zinc finger motifs of Nei/Fpg, which are of the C4 type [1].
• Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2 [4].

Biological context of NEIL2

• These results suggest that NEIL2 is involved in global genome repair mainly for removing oxidative products of cytosine [5].
• NEIL2 is similar to NEIL1 in having N-terminal Pro as the active site [5].
• In spite of their limited sequence homology, NEIL1 and NEIL2 interact with the same domains of Pol beta and Lig IIIalpha [6].
• The BER proteins including NEIL2, PNK, Pol beta, Lig IIIalpha and XRCC1 (but not APE1) could be isolated as a complex from human cells, competent for repair of 5-OHU in plasmid DNA [6].
• Lys49 and Lys153 were identified as the major acetylation sites in NEIL2 [7].

Associations of NEIL2 with chemical compounds

• Here we show that the NEIL2-initiated repair of 5-hydroxyuracil (5-OHU) similarly requires PNK [6].

Other interactions of NEIL2

• However, NEIL2 shows a unique preference for excising lesions from a DNA bubble, whereas NTH1 and OGG1 are only active with duplex DNA [4].
• CONCLUSION: We detected novel germline alterations in NEIL2, TDG and UNG patients with CRC [8].

References