Article
Biology
Roman Jaksik, David A. A. Wheeler, Marek Kimmel
Summary: This study proposes a method of detecting ORI based on somatic mutation patterns caused by the mutator phenotype of damaged DNA polymerase epsilon (POLE), and identifies shared ORI locations in tumors through accumulated mutations. The study also compares the results from multiple detection methods and defines a consensus set of ORI. The results demonstrate the viability of mutation-based detection in determining ORI location and associated sequence features.
Article
Multidisciplinary Sciences
Andrey G. Baranovskiy, Nigar D. Babayeva, Alisa E. Lisova, Lucia M. Morstadt, Tahir H. Tahirov
Summary: This study focused on the structure and function of human DNA polymerase alpha (Pol alpha) in its interaction with a mismatched template:primer. It was found that Pol alpha has low affinity to DNA in the absence of deoxynucleotide triphosphate (dNTP), but shows higher selectivity for a correct duplex in the presence of cognate dNTP. The efficiency of Pol alpha in extending a T-C mismatch is significantly reduced. This research is important for understanding the mechanism of Pol alpha infidelity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Barbara Ben Yamin, Sana Ahmed-Seghir, Junya Tomida, Emmanuelle Despras, Caroline Pouvelle, Andrey Yurchenko, Jordane Goulas, Raphael Corre, Quentin Delacour, Nathalie Droin, Philippe Dessen, Didier Goidin, Sabine S. Lange, Sarita Bhetawal, Maria Teresa Mitjavila-Garcia, Giuseppe Baldacci, Sergey Nikolaev, Jean Charles Cadoret, Richard D. Wood, Patricia L. Kannouche
Summary: The study highlights the crucial role of DNA polymerase zeta in bypassing DNA damage and cell proliferation, as well as the significance of REV3L's interactions with heterochromatin components in maintaining chromosome stability.
Article
Multidisciplinary Sciences
Maurizio Righini, Justin Costa, Wei Zhou
Summary: DNA molecular combing is a technique that stretches individual DNA molecules into a parallel configuration on a surface for sequencing. A novel approach has been introduced to address challenges such as overstretching and enzymatic access limitations, by attaching DNA molecules to a removable surface with tunable stretching factor. This new platform shows promise for high-throughput sequencing of Mbp-long molecules and potential genomic applications.
Article
Biochemistry & Molecular Biology
Luisa B. Huber, Navpreet Kaur, Melanie Henkel, Virginie Marchand, Yuri Motorin, Ann E. Ehrenhofer-Murray, Andreas Marx
Summary: More than 170 posttranscriptional RNA modifications have been identified, including pseudouridine (psi) and queuosine (Q), which play important roles in translation regulation. Current detection methods rely on chemical treatment of RNA samples, but we have developed a RT-active DNA polymerase variant, RT-KTq I614Y, that can directly identify psi and Q sites without the need for chemical treatment. This method, combined with next-generation sequencing, provides a more efficient and accurate way to detect RNA modifications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Gilles Crevel, Stephen Kearsey, Sue Cotterill
Summary: Errors made by DNA polymerases contribute to natural variation and genome instability. Cancer-associated polymerase variants with mutations in the exonuclease domain highlight the importance of polymerase misincorporation in disease. An assay was developed to compare misincorporation rates of different polymerase variants, showing differences between them and identifying a preference for C-to-T transitions.
Article
Biochemistry & Molecular Biology
Chen-Yu Lo, Yang Gao
Summary: Research suggests that T7 polymerase plays a dominant role in helicase-polymerase coupling and replisome progression. The helicase and polymerase sandwich the parental DNA, but only the polymerase carries the DNA with a positively charged cleft and stacks at the fork opening using a beta-hairpin loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Peter B. Bohall, Stephen D. Bell
Summary: The loss of putative repair polymerases PolB2 and/or PolB3 in the crenarchaeon Sulfolobus islandicus leads to a modest growth advantage and insensitivity to hydrogen peroxide. However, cells lacking PolB3 show enhanced sensitivity to the DNA damaging agent 4-NQO, suggesting that these non-essential DNA polymerases may influence DNA repair pathway choice in hyperthermophilic aerobes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Grant A. L. Bare, Gerald F. Joyce
Summary: Informational macromolecules in biology, such as nucleic acids and proteins, typically have specific chirality. However, recent research has shown that it is possible to amplify RNA molecules of opposite chirality using a specific enzyme, providing a potential for the evolution of cross-chiral RNA polymerases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Thomas A. Guilliam, Joseph T. P. Yeeles
Summary: The study shows that a yeast replisome is inherently tolerant to the oxidative lesion Tg, efficiently bypassing leading-strand Tg even in the absence of TLS machinery. A switch from Pol epsilon to Pol delta after helicase-polymerase uncoupling promotes rapid, efficient, and error-free lesion bypass at physiological nucleotide levels. Replicase switching may facilitate continued leading-strand synthesis when Pol delta is more effective at bypassing damage than Pol epsilon.
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Dean Huang, Anna E. Johnson, Brandon S. Sim, Teresa W. Lo, Houra Merrikh, Paul A. Wiggins
Summary: Quantitative characterization of nucleic-acid-bound molecular motors' dynamics in living cells is crucial for understanding the mechanistic basis of the central dogma. Lag-time analysis was developed to measure in vivo dynamics, providing quantitative locus-specific measurements of fork velocity and replisome pause durations. The observed dynamics are both locus and time dependent, even in wild-type cells, showing locus-specific pauses and temporal fork velocity oscillations.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Marina A. Bellani, Althaf Shaik, Ishani Majumdar, Chen Ling, Michael M. Seidman
Summary: The replication apparatus faces challenges in duplicating the genome, particularly when encountering covalent DNA adducts on the leading template strand. The helicase, a key component of the replication machinery, is responsible for unwinding DNA and coming into contact with the adducts. Recent studies have shown that the helicase is able to tolerate larger adducts than previously believed.
Article
Multidisciplinary Sciences
Monika Olahova, Bradley Peter, Zsolt Szilagyi, Hector Diaz-Maldonado, Meenakshi Singh, Ewen W. Sommerville, Emma L. Blakely, Jack J. Collier, Emily Hoberg, Viktor Stranecky, Hana Hartmannova, Anthony J. Bleyer, Kim L. McBride, Sasigarn A. Bowden, Zuzana Korandova, Alena Pecinova, Hans-Hilger Ropers, Kimia Kahrizi, Hossein Najmabadi, Mark A. Tarnopolsky, Lauren I. Brady, K. Nicole Weaver, Carlos E. Prada, Katrin Ounap, Monica H. Wojcik, Sander Pajusalu, Safoora B. Syeda, Lynn Pais, Elicia A. Estrella, Christine C. Bruels, Louis M. Kunkel, Peter B. Kang, Penelope E. Bonnen, Tomas Mracek, Stanislav Kmoch, Grainne S. Gorman, Maria Falkenberg, Claes M. Gustafsson, Robert W. Taylor
Summary: Variants in the POLRMT gene lead to defective mitochondrial transcription, causing mitochondrial disease-related phenotypes. Researchers have demonstrated this important disease mechanism through in vivo and in vitro experiments.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sebastian Zeltzer, Pierce Longmire, Marek Svoboda, Giovanni Bosco, Felicia Goodrum
Summary: Human cells have multiple specialized DNA polymerases for chromosomal DNA synthesis and repair, while complex DNA viruses may rely on host polymerases for synthesis. This study shows that error-prone Y-family polymerases can restrict human cytomegalovirus genome synthesis, while other TLS polymerases are required for optimal replication. Host polymerases also suppress viral genome rearrangements, indicating their role in ensuring viral genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
