PCNA-Dependent Long Patch Base Excision Repair

Stable Identifier
Homo sapiens
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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.

Bohr, VA, Kenny, MK, Dianov, GL, Jensen, BR

Biochemistry 1999
9780000 Mammalian base excision repair by DNA polymerases delta and epsilon

Dogliotti, E, Hübscher, U, Wilson, SH, Fortini, P, Pascucci, B, Parlanti, E, Stucki, M

Oncogene 1998
11250913 Human DNA polymerase beta initiates DNA synthesis during long-patch repair of reduced AP sites in DNA.

Podust, VN, Podlutsky, AJ, Dianova, II, 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, Bambara, RA, Tom, S

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).

Lindahl, T, Klungland, A

EMBO J 1997
10559261 Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified human proteins.

Tomkinson, AE, Hurwitz, J, Matsumoto, Y, Levin, DS, Park, MS, Kim, K, Gary, R

J Biol Chem 1999
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