3w0f

Structural highlights

Function

NEIL3_MOUSE DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). 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. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Liu M, Bandaru V, Bond JP, Jaruga P, Zhao X, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS. The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4925-30. doi:, 10.1073/pnas.0908307107. Epub 2010 Feb 25. PMID:20185759 doi:http://dx.doi.org/10.1073/pnas.0908307107
2. ↑ Sejersted Y, Hildrestrand GA, Kunke D, Rolseth V, Krokeide SZ, Neurauter CG, Suganthan R, Atneosen-Asegg M, Fleming AM, Saugstad OD, Burrows CJ, Luna L, Bjoras M. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18802-7. doi:, 10.1073/pnas.1106880108. Epub 2011 Nov 7. PMID:22065741 doi:http://dx.doi.org/10.1073/pnas.1106880108
3. ↑ Liu M, Bandaru V, Holmes A, Averill AM, Cannan W, Wallace SS. Expression and purification of active mouse and human NEIL3 proteins. Protein Expr Purif. 2012 Jul;84(1):130-9. doi: 10.1016/j.pep.2012.04.022. Epub, 2012 May 5. PMID:22569481 doi:http://dx.doi.org/10.1016/j.pep.2012.04.022
4. ↑ Regnell CE, Hildrestrand GA, Sejersted Y, Medin T, Moldestad O, Rolseth V, Krokeide SZ, Suganthan R, Luna L, Bjoras M, Bergersen LH. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Cell Rep. 2012 Sep 27;2(3):503-10. doi: 10.1016/j.celrep.2012.08.008. Epub 2012, Sep 6. PMID:22959434 doi:http://dx.doi.org/10.1016/j.celrep.2012.08.008
5. ↑ Rolseth V, Krokeide SZ, Kunke D, Neurauter CG, Suganthan R, Sejersted Y, Hildrestrand GA, Bjoras M, Luna L. Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress. Biochim Biophys Acta. 2013 May;1833(5):1157-64. doi:, 10.1016/j.bbamcr.2012.12.024. Epub 2013 Jan 7. PMID:23305905 doi:http://dx.doi.org/10.1016/j.bbamcr.2012.12.024
6. ↑ Liu M, Imamura K, Averill AM, Wallace SS, Doublie S. Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA. Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan, 9. PMID:23313161 doi:http://dx.doi.org/10.1016/j.str.2012.12.008