POLD1 gene is 33.7 kb long and composed of 1 non-coding exon followed by 25 coding exons and one last exon with both coding and 3 UTR regions.

The length of the transcript is 3444 bp and results in a protein of 1107 residues.

There is a pseudogene in chr 6q13 (LOC100422453).

The POLD1 gene encodes for p125 which is one of the four subunits that form Polδ (DNA polymerase delta) together with POLD2, POLD3 and POLD4 genes. This protein is one of the main DNA replicases in eukaryotes and is responsible of the replication of the lagging strand. POLD1 contains both the catalytic active site and the proofreading exonuclease domain (residues 245-571). Accordingly, the POLD1 gene confers to Polδ both replicative and 3 to 5 repair capabilities for the new strand.

Broadly expressed.

Nuclear.

Polδ is responsible of the polymerization of the lagging strand during DNA replication in yeast and humans. It also possesses 3 to 5 exonuclease capability to repair missincorporated nucleotides during DNA replication. Polδ is also involved in DNA repair pathways such as mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) or double-strand break repair.

A few missense germline mutations in the proofreading domain of POLD1 have been shown to be pathogenic such as D316G/H, P327L, R409W, L474P or S478N. These are extremely rare in the population and affect the exonuclease repair of Polδ hence resulting in a mutation rate increase of about 100-fold. Accordingly, these tumours are usually called ultramutated.

Although some somatic mutations in POLD1 have been reported for different tumour types, most of them are very likely to be passengers. They are usually found either in non-hypermutated tumours or in hypermutated tumours due to mismatch repair deficiency. So far no POLD1 somatic mutation has clearly been shown to be pathogenic.