POLD4

The DNA polymerase delta complex is involved in DNA replication and repair, and it consists of the proliferating cell nuclear antigen (PCNA; MIM 176740), the multisubunit replication factor C (see MIM 102579), and the 4 subunit polymerase complex: POLD1 (MIM 174761), POLD2 (MIM 600815), POLD3 (MIM 611415), and POLD4 (Liu and Warbrick, 2006 [PubMed 16934752]).[supplied by OMIM

Full Name

polymerase (DNA-directed), delta 4

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).

Biological Process

DNA synthesis involved in DNA repairManual Assertion Based On ExperimentIBA:GO_Central
DNA-templated DNA replicationManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of endothelial cell proliferationIEA:Ensembl

Cellular Location

Nucleus
Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation.

PTM

Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:17317665, PubMed:16934752, 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).