Reactome | PCNA-Dependent Long Patch Base Excision Repair

PCNA-Dependent Long Patch Base Excision Repair

Stable Identifier

R-HSA-5651801

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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PCNA-Dependent Long Patch Base Excision Repair

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Long-patch base excision repair (BER) can proceed through PCNA-dependent DNA strand displacement synthesis by replicative DNA polymerases - DNA polymerase delta complex (POLD) or DNA polymerase epsilon (POLE) complex. The PCNA-dependent branch of long-patch BER may occur in cells in the S phase of the cell cycle, when the replication complexes that contain PCNA, POLD or POLE, RPA and RFC are available. POLB incorporates the first nucleotide at the 3'-end of APEX1-generated single strand break (SSB), thus displacing the damaged AP (abasic) dideoxyribose phosphate residue at the 5'-end of SSB (5'ddRP). PCNA is recruited to BER sites by APEX1 and flap endonuclease FEN1, and loaded onto damaged DNA by RFC. POLD and POLE in complex with PCNA continue the displacement DNA strand synthesis. FEN1 cleaves the displaced DNA strand with the AP residue (5'ddRP), and DNA ligase I (LIG1) ligates the multiple nucleotide patch at the 3' end of the SSB with the FEN1-processed 5'-end of the SSB (Klungland and Lindahl 1997, Stucki et al. 1998, Dianov et al. 1999, Matsumoto et al. 1999, Podlutsky et al. 2001, Dianova et al. 2001, Ranalli et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
10460157	Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell extracts. Dianov, GL, Jensen, BR, Kenny, MK, Bohr, VA	Biochemistry	1999
9780000	Mammalian base excision repair by DNA polymerases delta and epsilon Stucki, M, Pascucci, B, Parlanti, E, Fortini, P, Wilson, SH, Hübscher, U, Dogliotti, E	Oncogene	1998
11250913	Human DNA polymerase beta initiates DNA synthesis during long-patch repair of reduced AP sites in DNA. Podlutsky, AJ, Dianova, II, Podust, VN, Bohr, VA, Dianov, GL	EMBO J	2001
11601988	Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair Dianova, II, Bohr, VA, Dianov, GL	Biochemistry	2001
12200445	AP endonuclease 1 coordinates flap endonuclease 1 and DNA ligase I activity in long patch base excision repair. Ranalli, TA, Tom, S, Bambara, RA	J Biol Chem	2002
9214649	Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1). Klungland, A, Lindahl, T	EMBO J	1997
10559261	Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins. Matsumoto, Y, Kim, K, Hurwitz, J, Gary, R, Levin, DS, Tomkinson, AE, Park, MS	J Biol Chem	1999