DNA polymerase delta catalytic subunit (DPOD1) is an enzyme that is encoded in the human by the POLD1 gene, in the DNA polymerase delta complex.[5][6][7] DPOD1 is responsible for synthesizing the lagging strand of DNA, and has also been implicated in some activities at the leading strand (Figure 1). The DPOD1 subunit encodes both DNA polymerizing and exonuclease domains, which provide the protein an important second function in proofreading to ensure replication accuracy during DNA synthesis, and in a number of types of replication-linked DNA repair following DNA damage.
Germline mutations impairing activity of POLD1 have been implicated in several types of hereditary cancer, in some sporadic cancers, and in a developmental syndrome of premature aging, Mandibular hypoplasia, Deafness, and Progeroid features and Lipodystrophy (MDPL/MDP syndrome). Studies of POLD1 emphasize the importance of maintaining genomic stability to limit tumorigenesis. It is currently unclear whether the enhanced tumorigenesis associated with POLD1 defects is the result of increased base substitutions or due to fork collapse and production of DNA double strand breaks (DSBs).[7][8] Recent reviews have addressed important functions of POLD1.[7][8]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000062822 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038644 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "UniProt". www.uniprot.org. Retrieved 22 February 2024.
- ^ Chung DW, Zhang JA, Tan CK, et al. (December 1991). "Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene". Proceedings of the National Academy of Sciences of the United States of America. 88 (24): 11197–201. Bibcode:1991PNAS...8811197C. doi:10.1073/pnas.88.24.11197. PMC 53101. PMID 1722322.
- ^ a b c Prindle MJ, Loeb LA (December 2012). "DNA polymerase delta in DNA replication and genome maintenance". Environmental and Molecular Mutagenesis. 53 (9): 666–82. Bibcode:2012EnvMM..53..666P. doi:10.1002/em.21745. PMC 3694620. PMID 23065663.
- ^ a b Rayner E, van Gool IC, Palles C, et al. (January 2016). "A panoply of errors: polymerase proofreading domain mutations in cancer". Nature Reviews. Cancer. 16 (2): 71–81. doi:10.1038/nrc.2015.12. PMID 26822575. S2CID 9359891.