POLD3
Description
The POLD3 (DNA polymerase delta 3, accessory subunit) is a protein-coding gene located on chromosome 11.
DNA polymerase delta subunit 3 is an enzyme that in humans is encoded by the POLD3 gene. It is a component of the DNA polymerase delta complex.
POLD3 is an essential component of both the DNA polymerase delta (Pol-delta) and DNA polymerase zeta (Pol-zeta) complexes, playing a crucial role in various DNA replication and repair processes. As part of the trimeric and tetrameric Pol-delta complexes (Pol-delta3 and Pol-delta4, respectively), POLD3 contributes to high-fidelity genome replication, particularly in lagging strand synthesis and repair. Its presence is critical for optimal Pol-delta activity, stabilizing the complex and facilitating its activation by PCNA. Pol-delta3 and Pol-delta4 exhibit distinct catalytic properties, with Pol-delta3 demonstrating higher proofreading activity compared to Pol-delta4. Both Pol-delta3 and Pol-delta4 are involved in processing Okazaki fragments in vitro, but Pol-delta3 appears better suited for this task due to its near-absence of strand displacement activity. This characteristic helps prevent gap formation during replication. In collaboration with DNA polymerase kappa, Pol-delta participates in nucleotide excision repair (NER) following UV irradiation. POLD3, in conjunction with PCNA and the RFC1 complex, facilitates the recruitment of POLD1, the catalytic subunit of Pol-delta, to damaged DNA sites. Under conditions of replication stress, POLD3 plays a vital role in the repair of broken replication forks through break-induced replication (BIR). Additionally, POLD3 is involved in translesion synthesis (TLS), enabling Pol-delta4 to bypass lesions like O6-methylguanine or abasic sites, independent of Pol-zeta or Pol-eta. This process facilitates bypass of abasic sites by Pol-delta by promoting extension from the nucleotide inserted opposite the lesion. Furthermore, POLD3 contributes to TLS as a component of the tetrameric Pol-zeta complex. Together with POLD2, it significantly enhances the efficiency and processivity of DNA synthesis by Pol-zeta compared to the minimal zeta complex consisting only of REV3L and REV7. POLD3 directly interacts with POLD2 within the tetrameric Pol-delta complex, contributing to the complex's overall function.
POLD3 is also known as IMD122, P66, P68, PPP1R128.
Associated Diseases
- ovarian cancer
- adult acute lymphoblastic leukemia
- breast cancer
- pancreatic ductal adenocarcinoma
- extranodal nasal NK/T cell lymphoma
