Identification of a Novel Protein, PDIP38, That Interacts with the p50 Subunit of DNA Polymerase δ and Proliferating Cell Nuclear Antigen

Liu, Li; Rodriguez-Belmonte, Esther M.; Mazloum, Nayef; Xie, Bin; Lee, Marietta Y.W.T.

doi:10.1074/jbc.m208694200

Cited by 98 publications

(134 citation statements)

References 34 publications

(53 reference statements)

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“…Thus, this provided the earliest proposed mechanism for the direct inhibition of Pol d activity in response to DNA damage. p21 interacts with Pol d as well as to PCNA; this binding occurs via the p50 subunit [Liu et al, 2003;Li et al, 2006a]. p21 levels are transcriptionally upregulated by the activation of p53 in response to DNA damage [Soria and Gottifredi, 2010].…”

Section: Connections Between P12 and P21çp21as A Regulator Of Pol D Amentioning

confidence: 99%

Regulation of human DNA polymerase delta in the cellular responses to DNA damage

Lee

Zhang

Lin

et al. 2012

Environ and Mol Mutagen

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The p12 subunit of polymerase delta (Pol d) is degraded in response to DNA damage induced by UV, alkylating agents, oxidative, and replication stresses. This leads to the conversion of the Pol d4 holoenzyme to the heterotrimer, Pol d3. We review studies that establish that Pol d3 formation is an event that could have a major impact on cellular processes in genomic surveillance, DNA replication, and DNA repair. p12 degradation is dependent on the apical ataxia telangiectasia and Rad3 related (ATR) kinase and is mediated by the ubiquitin-proteasome system. Pol d3 exhibits properties of an ''antimutator'' polymerase, suggesting that it could contribute to an increased surveillance against mutagenesis, for example, when Pol d carries out bypass synthesis past small base lesions that engage in spurious base pairing. Chromatin immunoprecipitation analysis and examination of the spatiotemporal recruitment of Pol d to sites of DNA damage show that Pol d3 is the primary form of Pol d associated with cyclobutane pyrimidine dimer lesions and therefore should be considered as the operative form of Pol d engaged in DNA repair. We propose a model for the switching of Pol d with translesion polymerases, incorporating the salient features of the recently determined structure of monoubiquitinated proliferating cell nuclear antigen and emphasizing the role of Pol d3. Because of the critical role of Pol d activity in DNA replication and repair, the formation of Pol d3 in response to DNA damage opens the prospect that pleiotropic effects may ensue. This opens the horizons for future exploration of how this novel response to DNA damage contributes to genomic stability. Environ. Mol. Mutagen. 53:683-698, 2012. V V C 2012 Wiley Periodicals, Inc.

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Section: Connections Between P12 and P21çp21as A Regulator Of Pol D Amentioning

confidence: 99%

Regulation of human DNA polymerase delta in the cellular responses to DNA damage

Lee

Zhang

Lin

et al. 2012

Environ and Mol Mutagen

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“…Interestingly, p21, together with two other proteins, PDIP38 and PDIP46 were found to interact with p50. 25 Here we report evidence for a direct interaction between p21 and the p50 subunit of human pol δ and for the possible physiological significance of this interaction.…”

Section: Introductionmentioning

confidence: 73%

“…p21 was unexpectedly found to interact with p50 together with two other proteins, PDIP38 and PDIP46. 25 Since the positive interaction in the yeast pair-wise assay could be due to bridging by a yeast protein, ELISA was used to determine if the interaction between p50 and p21 is direct in vitro (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

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Direct Interaction of p21 with p50, the Small Subunit of Human DNA Polymerase Delta

Xie²,

Rahmeh³

et al. 2006

Cell Cycle

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Previously published online as a Cell Cycle E-publication: http://www.landesbioscience.com/journals/cc/abstract.php?id=2425 KEY WORDS ReportDirect Interaction of p21 with p50, the Small Subunit of Human DNA Polymerase Delta ABSTRACT Using a yeast two-hybrid screening technique and the p50 subunit of human DNA polymerase delta (pol δ) as a bait, p21 was found to interact with the p50 subunit of pol δ. A direct interaction between p21 and p50 was confirmed by using ELISA and pull-down assays with purified proteins. The interaction sites between p50 and p21 were mapped by pull down assays with GST deletion mutants. Residues 127-193 constitute the primary interaction region on p50 to which p21 binds, while p50 binds to the C-terminal 26 residues of p21. A histone kinase activity was associated with the highly purified calf thymus pol δ and addition of purified recombinant p21 inhibited the kinase activity in a dose dependent manner. p50 is phosphorylated in vivo and can be phosphorylated by CDK2/cyclinA in vitro. In vivo evidence of p21 association with p50 was obtained by coimmunoprecipitation using MCF7 cells. It was also shown that the association of p21 with p50 and other components of the pol δ complex increased in MCF7 cells treated with adriamycin. Our results suggested that p50 might target or anchor p21 to pol δ complex upon certain DNA damage such as adriamycin treatment.

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“…As previously mentioned in Cellular Roles of DNA Polymerases of this review, in addition to carrying out the replication of chromosomal DNA, Pol d takes part in gap-filling during long-patch BER, NER, MMR and double strand break repair. The Pol d complex interacts with different proteins including POLD4, PCNA, RFC1, p21, WRN, p36, and p38 [Zhang et al, 1999;KamathLoeb et al, 2000;Liu et al, 2003;Wang et al, 2011;Rameh et al, 2012]. The catalytic subunit of mouse Pol d is encoded by the Pold1 gene, which has 85% similarity to human POLD1and maps to chromosome 7.…”

Section: Dna Polymerase Delta (Pol D)mentioning

confidence: 99%

Mouse models of DNA polymerases

Menezes¹,

Sweasy²

2012

Environ and Mol Mutagen

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In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells that belong to four different families. These DNA polymerases function in many different cellular processes including DNA replication, DNA repair, and damage tolerance. Several biochemical and cell biological studies have provoked a further investigation of DNA polymerase function using mouse models in which polymerase genes have been altered using gene-targeting techniques. The phenotypes of mice harboring mutant alleles reveal the prominent role of DNA polymerases in embryogenesis, prevention of premature aging, and cancer suppression. Environ. Mol. Mutagen. 53:645-665, 2012. V V C 2012 Wiley Periodicals, Inc.

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Identification of a Novel Protein, PDIP38, That Interacts with the p50 Subunit of DNA Polymerase δ and Proliferating Cell Nuclear Antigen

Cited by 98 publications

References 34 publications

Regulation of human DNA polymerase delta in the cellular responses to DNA damage

Regulation of human DNA polymerase delta in the cellular responses to DNA damage

Direct Interaction of p21 with p50, the Small Subunit of Human DNA Polymerase Delta

Mouse models of DNA polymerases

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