DNA polymerase delta subunit 2
Also known as: POLD2
Function
Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex. As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also 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. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex. Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7.
Classification
- Family (Pfam)
- PF18018 DNA_pol_D_N, PF04042 DNA_pol_E_B
- InterPro
- DNA_pol_a/d/e_bsu, DNA_pol_D_N, DNA_pol_delta/II_ssu, PolD2_C
- Functional cluster
- Zinc-Finger Nucleic-Acid-Binding & Methyltransferases
Experimental structures · PDB · 7
A predicted model is available from AlphaFold.
Gene Ontology · 11
- GO:0043625 delta DNA polymerase complex
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0016035 zeta DNA polymerase complex
- GO:0003677 DNA binding
- GO:0071897 DNA biosynthetic process
- GO:0006281 DNA repair
- GO:0006260 DNA replication
- GO:0006271 DNA strand elongation involved in DNA replication
- GO:0006261 DNA-templated DNA replication
- GO:0042276 error-prone translesion synthesis
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 2 0.99
- DNA polymerase delta subunit 2 0.99
- DNA polymerase delta subunit 2 0.96
- DNA polymerase delta small subunit 0.89
- DNA polymerase delta subunit 2 0.88
- DNA polymerase delta small subunit 0.85
- DNA polymerase delta subunit 2 0.84
- DNA polymerase subunit delta-2 0.75
- Probable DNA polymerase delta small subunit 0.71
- DNA polymerase epsilon subunit B 0.69
- DNA polymerase delta small subunit 0.69
- DNA polymerase epsilon subunit 2 0.67
Co-cited proteins · studied together in the literature
- DNA polymerase delta subunit 3 14 shared papers
- DNA polymerase delta catalytic subunit 14 shared papers
- DNA polymerase delta subunit 4 11 shared papers
- DNA polymerase delta subunit 2 1 shared papers
- DNA polymerase delta catalytic subunit 2 shared papers
- BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 1 1 shared papers
- ATPase WRNIP1 1 shared papers
- DNA polymerase eta 2 shared papers
- DNA polymerase zeta catalytic subunit 1 shared papers
- Chromosome transmission fidelity protein 18 homolog 1 shared papers
- DNA sliding clamp PCNA 3 shared papers
- DNA polymerase epsilon catalytic subunit A 1 shared papers
Literature · 27 cited papers
- Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress. J. Clin. Invest. · 2019
- Human Pol zeta purified with accessory subunits is active in translesion DNA synthesis and complements Pol eta in cisplatin bypass. Proc. Natl. Acad. Sci. U.S.A. · 2014
- Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science · 2014
- Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase delta. DNA Repair · 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
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
- Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage. Cell Cycle · 2012
- Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis. Biochemistry · 2010
- Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol. Cell · 2010
- … and 15 more in the literature graph