Alt. symbols: POLD | CDC2

Approved name: DNA polymerase delta 1, catalytic subunit
Alt. names: polymerase (DNA directed), delta 1, catalytic subunit (125kD), polymerase (DNA) delta 1, catalytic subunit | CDC2 homolog (S. cerevisiae)

Location: 19q13.33: 50384204 - 50418018 (+)
Gene type: protein_coding, 16 transcripts.

Scores: LoFtool: 0.656000 | pLI: 0.00180701 | LOEUF: 0.527

HGNC: 9175

NCBI: 5424, RefSeq: NG_033800.1

Ensembl: ENSG00000062822.16

LRG_785 | Status: public

OMIM: 174761

Expression | ProteinAtlas

POLD1 encodes the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex). As part of these complexes, the protein plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PMID:16510448, PMID:19074196, PMID:20334433, PMID:24035200, PMID:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). DPOD1_HUMAN,P28340

Genetic Variants in POLD1 have been associated wiht Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome [MIM:615381] | {Colorectal cancer, susceptibility to, 10} [MIM:612591]. More recently a homozigous missense mutation (c. 3178C>T; p.R1060C) in POLD1 has been identified in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation [PMID: 31629014]. [Load More]