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Special Issue "Structural and Functional Aspects of DNA Polymerases"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 1 July 2019

Special Issue Editor

Guest Editor
Prof. Anthony J. Berdis

Department of Chemistry, SR 363, Cleveland State University, 2351 Euclid Avenue, Cleveland, OH 44115, USA
Website | E-Mail
Interests: DNA polymerases; DNA damage; mutagenesis; chemotherapy; cancer biology; synthetic biology; nucleoside analogs

Special Issue Information

Dear Colleagues,

During the process of DNA replication, DNA polymerases add mononucleotides into a growing primer using a DNA or RNA template to guide each incorporation event. While conceptually simple, this process is remarkably challenging due to the structural diversity in DNA and nucleotide substrates as well as in the number of DNA polymerases that are involved in the cellular replication of nuclear and mitochondrial DNA. In this Special Issue, we have asked international experts in this field to use their expertise to provide novel insights into the mechanism and structure of these important and enigmatic enzymes. The topics of this Special Issue include discussions on our current understanding of how high- and low-fidelity DNA polymerases replicate both normal and damaged DNA. Additional areas of interest focus on drug development, specifically toward generating potent and selective therapeutic agents against DNA polymerases involved in cancer and viral/bacterial infections. Finally, several articles will focus on current and emerging biotechnical methodologies including PCR and genomic sequencing. Collectively, this Special Issue will provide an outstanding collection of work highlighting the key principles in catalysis and fidelity of DNA polymerases, as well as how mutagenesis and pathological conditions can arise from defects in fidelity.  

Prof. Anthony J. Berdis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • DNA polymerases
  • fidelity
  • mutagenesis
  • translesion DNA synthesis
  • nucleotide analogs
  • DNA sequencing
  • anti-cancer agents
  • anti-viral agents
  • polymerase chain reaction

Published Papers (1 paper)

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Research

Open AccessArticle
Probing the Effect of Bulky Lesion-Induced Replication Fork Conformational Heterogeneity Using 4-Aminobiphenyl-Modified DNA
Molecules 2019, 24(8), 1566; https://doi.org/10.3390/molecules24081566
Received: 27 February 2019 / Revised: 14 April 2019 / Accepted: 17 April 2019 / Published: 20 April 2019
PDF Full-text (2244 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bulky organic carcinogens are activated in vivo and subsequently react with nucleobases of cellular DNA to produce adducts. Some of these DNA adducts exist in multiple conformations that are slowly interconverted to one another. Different conformations have been implicated in different mutagenic and [...] Read more.
Bulky organic carcinogens are activated in vivo and subsequently react with nucleobases of cellular DNA to produce adducts. Some of these DNA adducts exist in multiple conformations that are slowly interconverted to one another. Different conformations have been implicated in different mutagenic and repair outcomes. However, studies on the conformation-specific inhibition of replication, which is more relevant to cell survival, are scarce, presumably due to the structural dynamics of DNA lesions at the replication fork. It is difficult to capture the exact nature of replication inhibition by existing end-point assays, which usually detect either the ensemble of consequences of all the conformers or the culmination of all cellular behaviors, such as mutagenicity or survival rate. We previously reported very unusual sequence-dependent conformational heterogeneities involving FABP-modified DNA under different sequence contexts (TG1*G2T [67%B:33%S] and TG1G2*T [100%B], G*, N-(2′-deoxyguanosin-8-yl)-4′-fluoro-4-aminobiphenyl) (Cai et al. Nucleic Acids Research, 46, 6356–6370 (2018)). In the present study, we attempted to correlate the in vitro inhibition of polymerase activity to different conformations from a single FABP-modified DNA lesion. We utilized a combination of surface plasmon resonance (SPR) and HPLC-based steady-state kinetics to reveal the differences in terms of binding affinity and inhibition with polymerase between these two conformers (67%B:33%S and 100%B). Full article
(This article belongs to the Special Issue Structural and Functional Aspects of DNA Polymerases)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Conformation-Specific Replication Block and Mutagenicity from Bulky DNA Lesions
Authors: Bongsup Cho and Deyu Li
Affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
Email:
Abstract: Bulky DNA adducts often exist in multiple conformations that are slowly interconverted to one another. Different conformations have shown to lead to different kinetic and binding capacities, presumably resulting in different mutational consequences. Studies on conformation-specific replication block are lacking, probably due to the complex dynamic nature of DNA replication. Recently, we investigated sequence effects of bulky DNA lesions generated from carcinogenic arylamines. We utilized a combination of surface plasmon resonance (SPR) and HPLC-based steady-state kinetics as well as replication bypass and mutagenicity assays to study the conformational differences in vitro and in cell.

Title: Mammalian DNA polymerase kappa
Author: Penny J. Beuning
Affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States
Email: [email protected]; [email protected]
Abstract: DNA polymerase (pol) kappa is one of the four mammalian Y-family DNA polymerases, which are specialized for DNA lesion bypass. Pol kappa is efficient at copying DNA containing minor groove adducts and is inhibited by major groove adducts. Pol kappa is also able to extend from primer termini involved in base pairs with damaged template bases, leading to the suggestion that pol kappa plays a further specialized role in the extension step of translesion synthesis. Numerous cancer-associated SNPs have been identified in the pol kappa gene, some of which have improved lesion bypass capability and therefore could play a role in chemotherapy resistance. This review will discuss the specificity and activity of pol kappa and known variants.

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