NEIL3
Developmental stage
Up-regulated during early S phase of the cell cycle, and sustained through G/M phase. Low expression levels in quiescent cells.
Domain
The N-terminal region (2-281) contains the glycosylase and lyase activities.
The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.
Function
DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). No activity on 8-oxoG detected (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).
Sequence Similarities
Belongs to the FPG family.
Tissue Specificity
Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts.
Cellular localization
- Nucleus
- Chromosome
- Recruited to replication stress sites via interaction with ubiquitinated CMG helicase.
Alternative names
Endonuclease 8-like 3, DNA glycosylase FPG2, DNA glycosylase/AP lyase Neil3, Endonuclease VIII-like 3, Nei-like protein 3, NEIL3