DNA polymerase delta 1

DNA polymerase delta 1 refers to the 125 kDa catalytic subunit of DNA polymerase delta1. This polymerase is encoded by the POLD1 gene located on chromosome 19q13.3. DNA polymerase delta has both polymerase and 3'-5' exonuclease activity and plays a crucial role in DNA replication and repair.

DNA polymerase delta 1 plays a crucial role in high-fidelity genome replication, including lag-strand synthesis and repair, as a catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complex (Pol-delta4 complex). This polymetrase subunit exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (Ducoux M et al. 2001; Lang T et al. 2007). These require the presence of the accessory proteins pol-delta2/pol-delta3/pol-delata4 for full activity. Depending on the absence/presence of the DNA polymerases Pol-delta3/pol-delata4, differences in catalytic activity can be detected. Particularly striking is the higher proofreading activity in the context of Pol-delta3 compared to Pol-delta4 (Chea Jet al. 2012). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited for this task as it shows little strand displacement activity compared to Pol-delta4 and stalls upon encountering the 5'-blocking oligonucleotides. The idling process of Pol-delta3 can prevent the formation of a gap (Cazzalini O et al. 2014). Together with DNA polymerase kappa, DNA polymerase delta1 performs about half of nucleotide excision repair (NER) synthesis after UV irradiation. Under conditions of DNA replication stress, it can catalyze the repair of broken replication forks by break-induced replication (BIR) in the presence of POLD3 and POLD4 (Cazzalini O et al. 2014). Involved in translesion synthesis (TLS) of templates with O6-methylguanine, 8oxoG or abasic sites.

1. Cazzalini O et al. (2014) CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis. Nucleic Acids Res 42:8433-8448.
2. Jet al. (2012) . Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage. Cell Cycle 11:2885-2895.
3. Ducoux M et al. (2001) Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA-binding motif present in the third subunit of human DNA polymerase delta. J Biol Chem 276:49258-49266.
4. Lang T et al. (2007) The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation. Mol Cell Biol 27:5587-5596)