Y-family DNA polymerases and their role in tolerance of cellular DNA damage

Sale, Julian E.; Lehmann, Alan R.; Woodgate, Roger

doi:10.1038/nrm3289

Cited by 596 publications

(783 citation statements)

References 129 publications

(136 reference statements)

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“…With regard to the DDR to UV in S-phase cells, it is also necessary to consider the major role that is played by the DNA damage tolerance (DDT) pathway in which TLS (translesion) polymerases carry out bypass synthesis across bulky lesions Zhang et al, 2011;Sale et al, 2012]. The major lesions caused by UV are cyclobutane pyrimidine dimers (CPDs) and [6-4]pyrimidine-pyrimidone photoproducts (6-4PPs).…”

Section: Degradation Of P12 and The Conversion Of Pol D4 To Pol D3 Inmentioning

confidence: 99%

“…The prolonged stalling of replication forks can result in further damage from collapsed replication forks and incomplete replication, ultimately causing cell death [Saleh-Gohari et al, 2005;Andersen et al, 2008]. To avoid this, DDT mechanisms are activated, whereby translesion polymerases allow bypass synthesis across bulky lesions Zhang et al, 2011;Sale et al, 2012]. Translesion synthesis is triggered by monoubiquitination of PCNA [Hoege et al, 2002], which in turn functions to recruit Pol h in the case of UV damage and subsequent switching between Pol d and Pol h [Kannouche and Lehmann, 2006;Zhang et al, 2011].…”

Section: Degradation Of P12 and The Conversion Of Pol D4 To Pol D3 Inmentioning

confidence: 99%

“…DOI 10.1002/em The monoubiquitination of PCNA converts PCNA from a trivalent to a hexavalent platform for interacting with other proteins. Although we do not have structural information for the binding of a full-length TLS polymerase to ub-PCNA, it is noteworthy that Pol h has one UBZ motif and two PIP boxes, Pol ı has two UBM motifs and one PIP-box, and Pol j has two UBZ motifs and one PIP-box, all located in their extended C-terminal regions [Acharya et al, 2008;Ohmori et al, 2009;Sale et al, 2012]. On the other side of the coin, the p125, p68, and p12 subunits all bind to PCNA, and their binding motifs corresponding to PIP-box motifs have been identified [Zhang et al, 1999;Liu et al, 2000;Li et al, 2006b].…”

Section: Roles Of Pol D3 In Translesion Synthesis By Tls Polymerasesçmentioning

confidence: 99%

“…In addition, like Pol h, they possess binding motifs for Rev1 in their C-termini. Rev1 possesses two UBM motifs and interacts with Rev7, a subunit of the B-family TLS polymerase, Pol f [Sale et al, 2012]. Thus, the issue of the recruitment of the appropriate TLS polymerase to specific types of DNA damage is a remarkably complex problem.…”

Section: Roles Of Pol D3 In Translesion Synthesis By Tls Polymerasesçmentioning

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: Degradation Of P12 and The Conversion Of Pol D4 To Pol D3 Inmentioning

confidence: 99%

Section: Degradation Of P12 and The Conversion Of Pol D4 To Pol D3 Inmentioning

confidence: 99%

Section: Roles Of Pol D3 In Translesion Synthesis By Tls Polymerasesçmentioning

confidence: 99%

Section: Roles Of Pol D3 In Translesion Synthesis By Tls Polymerasesçmentioning

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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“…TLS polymerases can accurately bypass lesions such as bases subjected to oxidative damage, abasic sites, and bulky lesions such as nitrogen adducts [Andersen et al, 2008]. The involvement of translesion polymerases in DNA damage tolerance pathways has been extensively reviewed by Prakash et al [2005], Waters et al [2009], and Sale et al [2012]. The main TLS polymerases are the Y family polymerases Pol h, Pol j, Pol ı, Rev1, and the B family polymerase Pol f [Ohmori et al, 2009;Choi et al, 2010].…”

Section: Dna Damage Tolerancementioning

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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DNAReplication: Mammalian

Smith

Hickey

et al. 2014

Encyclopedia of Life Sciences

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Deoxyribonucleic acid (DNA) replication is an evolutionarily semi‐conserved process that involves a mechanism to unwind the parent DNA strand, the synthesis of identical daughter strands, and steps to terminate the sequence. Owing to the massive amount of genetic information needed to be copied error‐free, the replication of DNA within the mammalian chromosome is highly complex, requiring the simultaneous firing of multiple origins and processing of DNA at defined sites within the cells. This action requires the strict regulation and precise timing of numerous proteins, enzymes and substrates. These components critical to DNA replication will associate within these compartments in the cell to form replication factories during processing. Although many of the basic functions of DNA synthesis are well‐defined, there is still much yet to be understood regarding the machinery involved in the initiation, synthesis and termination of mammalian DNA replication. Key Concepts: Mammalian DNA replication occurs at specific regions within the cell. Proteins necessary for DNA replication come together to form ‘replication factories’ within the nucleus. The manner and timing of mammalian DNA replication is largely determined in G1 of the cell cycle. The selection and timing of each replication site is controlled by a combination of primary sequences, kinase activation, transcription, and local chromatin environment. The proteins thus far identified at the mammalian cell DNA replication fork include the MCM helicase complex, DNA pol α‐primase, PCNA, RFC, DNA pol δ, FEN1, RPA, DNA ligase I, topoisomerase I and II and RNAse H. Termination of mammalian DNA replication is thought to be dependent on physical barriers within the replication factories, as opposed to actual termination sequences within the DNA structure. In the event of replication fork stalling, repair pathways must be activated to halt cell cycle progression and repair the damage.

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Y-family DNA polymerases and their role in tolerance of cellular DNA damage

Cited by 596 publications

References 129 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

Mouse models of DNA polymerases

DNAReplication: Mammalian

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