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Details on Person UniProt:Q9HCU8 POLD4
| Class:Id | ReferenceGeneProduct:89303 |
|---|---|
| _chainChangeLog | chain:1-107 added on Fri February 6 2015 |
| _displayName | UniProt:Q9HCU8 POLD4 |
| _timestamp | 2024-11-03 20:18:49 |
| chain | chain:1-107 |
| checksum | 6F412738E4D9A19C |
| comment | 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 (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). 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 (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480).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 DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:16510448, PubMed:17317665, PubMed:22801543). Within this complex, directly interacts with POLD1 and POLD2 (PubMed:12403614, PubMed:16510448). Directly interacts with PCNA, as do POLD1 and POLD3; this interaction stimulates Pol-delta4 polymerase activity (PubMed:24022480). As POLD1 and POLD2, 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 (PubMed:15670210). Upon genotoxic stress induced by DNA damaging agents or by replication stress, POLD4 is proteolytically degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) which has an increased proofreading activity (PubMed:17317665, PubMed:22801543). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).INTERACTION Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation.ALTERNATIVE PRODUCTS Expression is cell cycle-dependent, with highest levels in G2/M phase and a drastic drop in S phase (PubMed:22801543, PubMed:23913683). This trough may be mediated by DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2))-mediated proteasomal degradation (PubMed:23913683).INDUCTION In response to DNA damage, genotoxic stress and replication stress, following UV irradiation, ionizing radiation, treatment with methyl methanesulfonate, hydroxyurea, or with aphidicolin, protein expression drops to undetectable levels, due to proteasomal degradation (PubMed:17317665, PubMed:22801543, PubMed:23233665, PubMed:23913683, PubMed:24300032). This down-regulation is ATR-dependent (PubMed:17317665).PTM Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:16934752, PubMed:17317665, PubMed:23233665, PubMed:23913683). This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)) (PubMed:23233665, PubMed:24022480). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage (PubMed:24022480).SIMILARITY Belongs to the DNA polymerase delta subunit 4 family. |
| description | recommendedName: DNA polymerase delta subunit 4 alternativeName: DNA polymerase delta subunit p12 |
| geneName | POLD4 POLDS |
| identifier | Q9HCU8 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing DNA damage DNA excision DNA repair DNA replication Nucleus Proteomics identification Reference proteome Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | POLD4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9000555] ENSEMBL:ENSG00000175482 POLD4 [Homo sapiens] |
| secondaryIdentifier | DPOD4_HUMAN F5H506 |
| sequenceLength | 107 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8971894] UniProt:Q9HCU8-1 POLD4 [Homo sapiens] [ReferenceIsoform:8971895] UniProt:Q9HCU8-2 POLD4 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:68447] POLD4 [nucleoplasm] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q9HCU8 POLD4 (89303)
