DNA polymerase delta subunit 4
Also known as: POLD4, POLDS
Function
As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity. Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb. Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites. Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival.
Classification
- Family (Pfam)
- PF04081 DNA_pol_delta_4
- InterPro
- DNA_pol_delta_4
- Functional cluster
- Eukaryotic Transcription Factors & related
Experimental structures · PDB · 7
A predicted model is available from AlphaFold.
Gene Ontology · 4
Drugs targeting this protein · 6
- FLUDARABINE PHOSPHATE inhibitor
- GEMCITABINE HYDROCHLORIDE inhibitor
- CLOFARABINE inhibitor
- TROXACITABINE inhibitor
- ASPACYTARABINE inhibitor
- CYTARABINE inhibitor
Related proteins · sequence + function similarity
- DNA polymerase delta subunit 4 0.95
- DNA polymerase delta subunit 4 0.90
- ATP-dependent DNA helicase Q4 0.79
- UPF0575 protein C19orf67 0.78
- Protein phosphatase 1 regulatory subunit 35 0.77
- Protein PERCC1 0.77
- Protein PERCC1 0.77
- Protein phosphatase 1 regulatory subunit 35 0.76
- Coiled-coil domain-containing protein 24 0.76
- Protein INCA1 0.74
- Protein FAM180B 0.74
- Annexin-2 receptor 0.74
Co-cited proteins · studied together in the literature
- DNA polymerase delta catalytic subunit 12 shared papers
- DNA polymerase delta subunit 3 11 shared papers
- DNA polymerase delta subunit 2 11 shared papers
- DNA polymerase delta subunit 4 1 shared papers
- DNA polymerase delta subunit 3 1 shared papers
- DNA polymerase delta subunit 4 1 shared papers
- DNA polymerase delta catalytic subunit 2 shared papers
- DNA polymerase delta subunit 2 1 shared papers
- ATPase WRNIP1 1 shared papers
- E3 ubiquitin-protein ligase RNF8 1 shared papers
- DNA polymerase eta 1 shared papers
- Polymerase delta-interacting protein 2 1 shared papers
Literature · 18 cited papers
- Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science · 2014
- The tail that wags the dog: p12, the smallest subunit of DNA polymerase delta, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression. Cell Cycle · 2014
- Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase delta. DNA Repair · 2013
- Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression after DNA damage. J. Biol. Chem. · 2013
- A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase delta in response to DNA damage and during the S phase. J. Biol. Chem. · 2013
- Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase delta for degradation in response to DNA damage. J. Biol. Chem. · 2013
- Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage. Cell Cycle · 2012
- The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis. Biochemistry · 2010
- DNA damage alters DNA polymerase delta to a form that exhibits increased discrimination against modified template bases and mismatched primers. Nucleic Acids Res. · 2009
- A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta. J. Biol. Chem. · 2007
- The p66 and p12 subunits of DNA polymerase delta are modified by ubiquitin and ubiquitin-like proteins. Biochem. Biophys. Res. Commun. · 2006
- Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
- … and 6 more in the literature graph