P97283 · DPOD1_MESAU
- ProteinDNA polymerase delta catalytic subunit
- GenePOLD1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1103 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), 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. 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. 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. 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, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites.
Miscellaneous
In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
Catalytic activity
- a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)
Cofactor
Note: Binds 1 [4Fe-4S] cluster.
Activity regulation
Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation. Stimulated in the presence of PCNA (By similarity).
This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).
This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 1008 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1011 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1022 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1025 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1054 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1057 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1067 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1072 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | delta DNA polymerase complex | |
Molecular Function | 4 iron, 4 sulfur cluster binding | |
Molecular Function | chromatin binding | |
Molecular Function | damaged DNA binding | |
Molecular Function | DNA-directed DNA polymerase activity | |
Molecular Function | exonuclease activity | |
Molecular Function | metal ion binding | |
Molecular Function | nucleotide binding | |
Biological Process | cellular response to UV | |
Biological Process | DNA replication | |
Biological Process | DNA synthesis involved in DNA repair | |
Biological Process | error-free translesion synthesis | |
Biological Process | fatty acid homeostasis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA polymerase delta catalytic subunit
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Mesocricetus
Accessions
- Primary accessionP97283
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with PCNA and POLD3 at S phase replication sites. After UV irradiation, recruited to DNA damage sites within 2 hours, independently on the cell cycle phase, nor on PCNA ubiquitination. This recruitment requires POLD3, PCNA and RFC1-replication factor C complex.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 64 | in delta' | ||||
Sequence: Missing | ||||||
Natural variant | 386 | in delta' | ||||
Sequence: P → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000046443 | 1-1103 | DNA polymerase delta catalytic subunit | |||
Sequence: MDFKRRQGPGPGVPPKRARGGLWDEDEPSQFEENLALLEEIEAENRLQEAEEELQLPPQGPAGGQFSTADIDPRWKRPALCALDPNTEPLIFQQLEIDHYVGSAVPLPGGPPTSCNSVPILRAFGVTDEGFSVCCHIHGFAPYFYTPAPPGFGAEHLSDLQRELSTAISRDQRGGKELSGPAVLAIELCSRESMFGYHGHGPSPFLRITLALPRLVAPARRLLEQGIRVPGLGTPSFAPYEANVDFEIRFMVDADIVGCNWLELPAGKYVWRTEKKATQCQLEVDVLWSDVISHPPEGQWQRIAPLRVLSFDIECAGRKGIFPEPERDPVIQICSLGLRWGEPEPFLRLALTLRPCAPILGAKVQSYEREEDLLQAWPNFILAMDPDVITGYNIQNFDLPYLISRAQTLKVDRFPFLGRVTGLRSNIRDSSFQSRQVGRRDSKVVSMVGRVQMDMLQVLLREHKLRSYTLNAVSFHFLGEQKEDVQHSIITDLQNGNEQTRRRLAVYCLRDAFLPLRLLERLMVLVNNVEMARVTGVPLGYLLSRGQQVKVVSQLLRQAMRQGLLMPVVKTEGGEDYTGATVIEPLKGYYDVPIATLDFSSLYPSIMMAHNLCYTTLLRPGAAQKLGLKPDEFIKTPTGDEFVKSSVRKGLLPQILENLLSARKRAKAELAQETDPLRRQVLDGRQLALKVSANSVYGFTGAEVGKLPCLEISQSVTGFGRQMIEKTKQLVESKYTLENGYNANAKVVYGDTDSVMCRFGVSSVAEAMSLGREAANWVSSHFPSPIRLEFEKVYFPYLLISKKRYAGLLFSSQPDTHDRMDCKGLEAVRRDNCPLVANLVTSSLRRILVDRDPDGAVAHAKDVISDLLCNRIDISQLVITKELTRAAADYAGKQAHVELAERMRKRDPGSAPSLGDRVPYVIIGAAKGVAAYMKSEDPLFVLEHSLPIDTQYYLGQQLAKPLLRIFEPILGEGRAESVLLRGDHTRCKTVLTSKVGGLLAFTKRRNCCIGCRSVINHQGAVCEFCQPRESELYQKEVSHLNALEERFSRLWTQCQRCQGSLHEDVICTSRDCPIFYMRKKVRKDLEDQERLLQRFGPPGPEAW | ||||||
Modified residue | 19 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Cross-link | 570 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Keywords
- PTM
Interaction
Subunit
Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD2 and POLD4. Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites. POLD1 displays different catalytic properties depending upon the complex it is found in. It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage. Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity. As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Also observed as a dimeric complex with POLD2 (Pol-delta2). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2. Interacts with CIAO1. Interacts with POLDIP2 (By similarity).
Interacts with RFC1 (By similarity).
Interacts with RFC1 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-29 | Disordered | ||||
Sequence: MDFKRRQGPGPGVPPKRARGGLWDEDEPS | ||||||
Motif | 4-19 | Nuclear localization signal | ||||
Sequence: KRRQGPGPGVPPKRAR | ||||||
Zinc finger | 1008-1025 | CysA-type | ||||
Sequence: CIGCRSVINHQGAVCEFC | ||||||
Motif | 1054-1072 | CysB motif | ||||
Sequence: CQRCQGSLHEDVICTSRDC |
Domain
The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.
Sequence similarities
Belongs to the DNA polymerase type-B family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,103
- Mass (Da)123,466
- Last updated1997-05-01 v1
- Checksum34AB5BF72DE53011
Keywords
- Technical term