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

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

Stable Identifier

R-HSA-5649702

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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

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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
16982218	NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells Karimi-Busheri, F, Wang, H, Weinfeld, M, Mitra, S, Hazra, TK, Kedar, P, Wilson, SH, Leppard, JB, Prasad, R, Boldogh, I, Tomkinson, AE, Wiederhold, L, Das, A	DNA Repair (Amst.)	2006
11163244	XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair Taylor, RM, Whitehouse, CJ, Weinfeld, M, Lasko, DD, Zhang, H, Thistlethwaite, A, Caldecott, KW, Karimi-Busheri, F	Cell	2001
15260972	AP endonuclease-independent DNA base excision repair in human cells Karimi-Busheri, F, Weinfeld, M, Mitra, S, Wiederhold, L, Izumi, T, Hazra, TK, Kedar, P, Wilson, SH, Leppard, JB, Prasad, R, Rasouli-Nia, A, Tomkinson, AE	Mol. Cell	2004