Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage

Chea, Jennifer; Zhang, Sufang; Zhao, Hong; Zhang, Zhongtao; Lee, Ernest Y.C.; Darzynkiewicz, Zbigniew; Lee, Marietta Y.W.T.

doi:10.4161/cc.21280

Cited by 34 publications

(71 citation statements)

References 64 publications

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“…A direct demonstration that Pol d3 is physically associated with CPD lesions was obtained by chromatin immunoprecipitation analysis using immobilized p125 antibody after irradiation of cells with UV [Chea et al, 2012]. The immunoprecipitates were analyzed by Western blotting for all four Pol d subunits; only p125, p68, and p50 were present, showing that Pol d3 is the primary form available for DNA repair and/or translesion synthesis under the conditions of the experiments.…”

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

“…The immunoprecipitates were analyzed by Western blotting for all four Pol d subunits; only p125, p68, and p50 were present, showing that Pol d3 is the primary form available for DNA repair and/or translesion synthesis under the conditions of the experiments. Because we used asynchronous cells, Pol d3 must be considered to be the form involved in CPD repair in all phases of the cell cycle [Chea et al, 2012].…”

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

“…We used the technique of irradiation through UV-opaque polycarbonate filters with 5-lm pores [Volker et al, 2001]. These gave rise to macrofoci that were readily observed and also allowed quantitative analysis of the percentage colocalization with CPD damage [Chea et al, 2012]. Examination of the time course of recruitment over a period of 0-4 hr after UV irradiation in A549 lung epithelial cells showed that the recruitment of all four subunits of Pol d reached a plateau within the first 2 hr.…”

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

“…1, ''5''). The incomplete degradation within the localized areas of damage compared to complete degradation during global UV irradiation can be explained by the lower amounts of DNA damage in the macrofoci, which could lead to reduced rates of overall nuclear p12 degradation coupled with exchange of Pol d3 [Chea et al, 2012].…”

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

“…Recruitment of ATR was near-complete within 30 min; recruitment of Pol h occurred more rapidly than p125 and peaked at about 80% by 1 hr after UV exposure. This can be compared to the recruitment of p125, which was near-complete by 2 hr [Chea et al, 2012].…”

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

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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: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

Section: Spatiotemporal Dynamics Of the Recruitment Of Pol D To Dna Dmentioning

confidence: 99%

See 3 more Smart Citations

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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Structure and function relationships in mammalian DNA polymerases

Hoitsma

Whitaker

Schaich

et al. 2019

Cell. Mol. Life Sci.

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DNA polymerases are vital for the synthesis of new DNA strands. Since the discovery of DNA polymerase I in Escherichia coli, a diverse library of mammalian DNA polymerases involved in DNA replication, DNA repair, antibody generation, and cell checkpoint signaling has emerged. While the unique functions of these DNA polymerases are differentiated by their association with accessory factors and/or the presence of distinctive catalytic domains, atomic resolution structures of DNA polymerases in complex with their DNA substrates have revealed mechanistic subtleties that contribute to their specialization. In this review, the structure and function of all 15 mammalian DNA polymerases from families B, Y, X, and A will be reviewed and discussed with special emphasis on the insights gleaned from recently published atomic resolution structures.

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Comparative proteomics analysis of global cellular stress responses to hydroxyurea-induced DNA damage in HeLa cells

et al. 2014

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Both environmental agents and spontaneous cellular events cause serious DNA damage, threatening the integrity of the genome. In response to replication stress or genotoxic agents triggered DNA damage, degradation of p12 subunit of DNA polymerase delta (Pol d) results in an inter-conversion between heterotetramer (Pol d4) and heterotrimer (Pol d3) forms and plays a significant role in DNA damage response in eukaryotic cells. In this work, we used mass spectrometry-based proteomic approach to identify those cellular stress response protein changes corresponding to the degradation of p12 in DNAdamaged HeLa cells by the treatment with hydroxyurea (HU). A total of 736 ± 13 proteins in non-treated control group and 741 ± 19 protein spots in HUtreated cells were detected, of which 34 proteins (17 up-regulated and 17 down-regulated) exhibited significantly altered protein expression levels. Their physiological roles are mainly associated with cellular components, molecular functions, and biological processes by gene ontology analysis, among which 21 proteins were mapped to KEGG pathways. They are involved in 5 primary pathways with the subsets involving 16 secondary pathways by further KEGG analysis. More interestingly, the up-regulation of translationally controlled tumor protein was further identified to be associated with p12 degradation by Western blot analysis. Our works may enlarge and broaden our view for deeply understanding how global cellular stress responds to DNA damage, which could contribute to the etiology of human cancer or other diseases that can result from loss of genomic stability.

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Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage

Cited by 34 publications

References 64 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

Structure and function relationships in mammalian DNA polymerases

Comparative proteomics analysis of global cellular stress responses to hydroxyurea-induced DNA damage in HeLa cells

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