Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism

Yang, Wei; Gao, Yang

doi:10.1146/annurev-biochem-062917-012405

Cited by 183 publications

(210 citation statements)

References 149 publications

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“…Crystal structures of TLS polymerases have been determined, providing a molecular basis for understanding their biochemical properties (reviewed by Yang and Woodgate. , Yang and Gao, ; Goodman and Woodgate, ).…”

Section: Tls Polymerasesmentioning

confidence: 99%

“…Crystal structures of TLS polymerases have been determined, providing a molecular basis for understanding their biochemical properties (reviewed by Woodgate. 2007, Yang andGao, 2018;Goodman and Woodgate, 2013). All three E. coli TLS polymerases interact with the β-clamp (Hughes et al, 1991;Sutton et al, 1999, Sutton andDuzen, 2006;Bunting et al, 2003;Patoli et al, 2013).…”

Section: Tls Polymerasesmentioning

confidence: 99%

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The SOS system: A complex and tightly regulated response to DNA damage

Masłowska

Makiela‐Dzbenska

Fijałkowska

2019

Environ and Mol Mutagen

300

212

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Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli , this inducible system is termed the SOS response. The SOS global regulatory network consists of multiple factors promoting the integrity of DNA as well as error‐prone factors allowing for survival and continuous replication upon extensive DNA damage at the cost of elevated mutagenesis. Due to its mutagenic potential, the SOS response is subject to elaborate regulatory control involving not only transcriptional derepression, but also post‐translational activation, and inhibition. This review summarizes current knowledge about the molecular mechanism of the SOS response induction and progression and its consequences for genome stability. Environ. Mol. Mutagen. 60:368–384, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

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Section: Tls Polymerasesmentioning

confidence: 99%

Section: Tls Polymerasesmentioning

confidence: 99%

The SOS system: A complex and tightly regulated response to DNA damage

Masłowska

Makiela‐Dzbenska

Fijałkowska

2019

Environ and Mol Mutagen

300

212

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“…The first crystal structures of the TdT polymerase and of binary complexes with either a primer or an incoming triphosphate were resolved in 2002 by Delarue et al . This analysis revealed that the overall structure of the TdT is quite rigid and similar to that of most other polymerases, as it presents the typical thumb, fingers, and palm elements. On the other hand, the presence of an unusual 16 amino acid long loop (called loop 1) adopting a lariat‐like structure is believed to hinder the accommodation of a templating strand and, thus, to account for the template specificity .…”

Section: Terminal Deoxynucleotidyl Transferasementioning

confidence: 99%

Terminal Deoxynucleotidyl Transferase in the Synthesis and Modification of Nucleic Acids

Sarac

Hollenstein

2019

ChemBioChem

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The terminal deoxynucleotidyl transferase (TdT) belongs to the X family of DNA polymerases. This unusual polymerase catalyzes the template‐independent addition of random nucleotides on 3′‐overhangs during V(D)J recombination. The biological function and intrinsic biochemical properties of the TdT have spurred the development of numerous oligonucleotide‐based tools and methods, especially if combined with modified nucleoside triphosphates. Herein, we summarize the different applications stemming from the incorporation of modified nucleotides by the TdT. The structural, mechanistic, and biochemical properties of this polymerase are also discussed.

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“…This modification promotes a switch from the replicative polymerase to specialized low-fidelity polymerases, which contain both PIP-boxes as well as ubiquitin-binding motifs, and thus preferentially bind to ubiquitinated PCNA ( Ubi PCNA) (Bienko et al, 2005;Choe and Moldovan, 2017;Guo et al, 2006;Hoege et al, 2002;Kannouche et al, 2004;Stelter and Ulrich, 2003). These specialized polymerases promote the bypass of replication obstacles in order to maintain efficient DNA-replication, a process known as translesion synthesis (TLS) (Vaisman and Woodgate, 2017;Yang and Gao, 2018).…”

Section: Introductionmentioning

confidence: 99%

PCNA ubiquitination protects stalled replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly

Thakar

Leung

Nicolae

et al. 2019

Preprint

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Upon genotoxic stress, PCNA ubiquitination allows for replication of damaged DNA by recruiting lesion-bypass DNA polymerases. However, PCNA is also ubiquitinated during normal S-phase progression. By employing ubiquitination-deficient 293T and RPE1 cells generated through CRISPR/Cas9 genome editing, we show that this modification promotes cellular proliferation and suppression of genomic instability under normal growth conditions. Loss of PCNA-ubiquitination results in DNA2-mediated but MRE11independent nucleolytic degradation of nascent DNA at stalled replication forks. This degradation is linked to defective gap-filling in the wake of the replication fork, and incomplete Okazaki fragment synthesis and maturation, thus interfering with efficient PCNA unloading by ATAD5 and subsequent nucleosomal deposition by CAF-1.Moreover, concomitant loss of PCNA-ubiquitination and BRCA2 results in a synergistic increase in nascent DNA degradation and sensitivity to PARP-inhibitors. In conclusion, we show that by ensuring efficient Okazaki fragment maturation, PCNA-ubiquitination protects fork integrity and promotes the resistance of BRCA-deficient cells to PARPinhibitors.

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Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism

Cited by 183 publications

References 149 publications

The SOS system: A complex and tightly regulated response to DNA damage

The SOS system: A complex and tightly regulated response to DNA damage

Terminal Deoxynucleotidyl Transferase in the Synthesis and Modification of Nucleic Acids

PCNA ubiquitination protects stalled replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly

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