DNA polymerase delta subunit 3

Definition:

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. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA. 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. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites. 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 tetrametric DNA polymerase zeta complex. Along with POLD2, 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.

References:

[1]. Hao Li, et al. Functional roles of p12, the fourth subunit of human DNA polymerase delta. J Biol Chem. 2006 May 26;281(21):14748-55. [Content Brief]

[2]. Jennifer Chea, et al. Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage. Cell Cycle. 2012 Aug 1;11(15):2885-95. [Content Brief]

[3]. Kouji Hirota, et al. In vivo evidence for translesion synthesis by the replicative DNA polymerase δ. Nucleic Acids Res. 2016 Sep 6;44(15):7242-50. [Content Brief]

[4]. Xiao Meng, et al. The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis. Biochemistry. 2010 May 4;49(17):3545-54. [Content Brief]

[5]. Sufang Zhang, et al. A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta. J Biol Chem. 2007 May 25;282(21):15330-40. [Content Brief]

[6]. Lorenzo Costantino, et al. Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science. 2014 Jan 3;343(6166):88-91. [Content Brief]

[7]. Tomoo Ogi, et al. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol Cell. 2010 Mar 12;37(5):714-27. [Content Brief]

[8]. Kouji Hirota, et al. The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ. Nucleic Acids Res. 2015 Feb 18;43(3):1671-83. [Content Brief]

[9]. Szu Hua Sharon Lin, et al. Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase δ. DNA Repair (Amst). 2013 Nov;12(11):922-35. [Content Brief]

[10]. Xiao Meng, et al. DNA damage alters DNA polymerase delta to a form that exhibits increased discrimination against modified template bases and mismatched primers. Nucleic Acids Res. 2009 Feb;37(2):647-57. [Content Brief]

[11]. Young-Sam Lee, et al. Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):2954-9. [Content Brief]

[12]. P Hughes, et al. Isolation and identification of the third subunit of mammalian DNA polymerase delta by PCNA-affinity chromatography of mouse FM3A cell extracts. Nucleic Acids Res. 1999 May 15;27(10):2108-14. [Content Brief]

[13]. J Mo, et al. Evidence that DNA polymerase delta isolated by immunoaffinity chromatography exhibits high-molecular weight characteristics and is associated with the KIAA0039 protein and RPA. Biochemistry. 2000 Jun 20;39(24):7245-54. [Content Brief]

[14]. M Ducoux, et al. Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA-binding motif present in the third subunit of human DNA polymerase delta. J Biol Chem. 2001 Dec 28;276(52):49258-66. [Content Brief]

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