POLD1 Gene

The POLD1 gene (POLD1 stands for "DNA polymerase delta 1, catalytic subunit") is a protein-coding gene located on chromosome 19q13.3.

The POLD1 gene encodes the 125 kDa catalytic subunit of DNA polymerase delta 1. This DNA polymerase has both polymerase and 3'-5' exonuclease activity and plays a crucial role in DNA replication and repair. Alternatively spliced transcript variants have been observed for the POLD1 gene. A pseudogene of this gene is located on the long arm of chromosome 6.

Diseases associated with POLD1 include:

• Mandibular hypoplasia, deafness, progeroid features and lipodystrophy syndrome (OMIM: 615381)
• and
• Colorectal cancer, susceptibility to, 10 (OMIM: 612591)

• A LOF mutation in POLD1 leads to an immunodeficiency syndrome (CID) (Conde CD et al. 2019; Cui Y et al. 2020)

Related signaling pathways include telomere C-strand synthesis (lagging strand) and transcription-coupled nucleotide excision repair (TC-NER).

As a catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complex (Pol-delta4 complex), it plays a crucial role in high-fidelity genome replication, including lagging strand synthesis and repair.

Together with DNA polymerase kappa, DNA polymerase delta 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 (see also under Translesion DNA Synthesis/TLS)

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)