APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway

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R-HSA-5649702
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Homo sapiens
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NEIL1 and NEIL2 have a dual DNA glycosylase and beta/delta lyase activity. The AP (apurinic/apyrimidinic) site-directed lyase activity of NEIL1 and NEIL2 is their major physiological role, as they can act on AP sites generated spontaneously or by other DNA glycosylases. NEIL1 or NEIL2 cleave the damaged DNA strand 5' to the AP site, producing a 3' phosphate terminus (3'Pi) and a 5' deoxyribose phosphate terminus (5'dRP). DNA polymerase beta (POLB) excises 5'dRP residue but is unable to add the replacement nucleotide to DNA with the 3'Pi end. PNKP, a DNA 3' phosphatase, removes 3'Pi and enables POLB to incorporate the replacement nucleotide, which is followed by ligation of repaired DNA strand by XRCC1:LIG3 complex (Whitehouse et al. 2001, Wiederhold et al. 2004, Das et al. 2006).

Literature References
PubMed ID Title Journal Year
11163244 XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair

Whitehouse, CJ, Taylor, RM, Thistlethwaite, A, Zhang, H, Karimi-Busheri, F, Lasko, DD, Weinfeld, M, Caldecott, KW

Cell 2001
16982218 NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells

Das, A, Wiederhold, L, Leppard, JB, Kedar, P, Prasad, R, Wang, H, Boldogh, I, Karimi-Busheri, F, Weinfeld, M, Tomkinson, AE, Wilson, SH, Mitra, S, Hazra, TK

DNA Repair (Amst.) 2006
15260972 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

Mol. Cell 2004
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