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
Genetics & Heredity
MaryElizabeth Stein, Suzanne E. Hile, Matthias H. Weissensteiner, Marietta Lee, Sufang Zhang, Eduard Kejnovsky, Iva Kejnovska, Kateryna D. Makova, Kristin A. Eckert
Summary: G-quadruplex structures can influence the accuracy of DNA polymerase during synthesis, especially during the synthesis of stable G-quadruplexes. The errors made by polymerase are associated with the topology and stability of the G-quadruplex structures.
Review
Biochemistry & Molecular Biology
Yaoqi Sun, Zhongping Cheng, Shupeng Liu
Summary: MCM2 plays a vital role in DNA replication and its dysfunction is associated with the occurrence and progression of multiple cancers. The altered expression of MCM2 can serve as a sensitive biomarker for cancer diagnosis, prognosis, and chemotherapy response. In addition, targeting MCM2 may improve the effect of tumor immunotherapy.
MOLECULAR MEDICINE
(2022)
Review
Oncology
Michal Gola, Przemyslaw Stefaniak, Janusz Godlewski, Barbara Alicja Jereczek-Fossa, Anna Starzynska
Summary: POLD1, a subunit of DNA polymerase delta complex, is crucial for DNA replication and repair. Its mutations have been found in various malignancies and its expression patterns have been associated with clinicopathological features. This review aims to summarize the current knowledge and future prospects of POLD1 in cancer research.
Article
Cell Biology
Zsolt Gyure, Adam Poti, Eszter Nemeth, Bernadett Szikriszt, Rita Lozsa, Michal Krawczyk, Andrea L. Richardson, David Szuts
Summary: Translesion DNA synthesis (TLS) using specialized DNA polymerases facilitates replication over damaged or difficult-to-replicate templates. Investigating three main TLS control mechanisms, REV1 and PCNA ubiquitylation recruit TLS polymerases while PRIMPOL creates post-replicative gaps. Whole-genome sequencing of human RPE-1 cell clones reveals REV1 and Polymerase z as responsible for base substitution mutagenesis resembling homologous recombination deficiency, while PRIMPOL-/- cells show reduced component resembling oxidative mutagenesis. Small deletions in short repeats appear in REV1-/-PCNAK164R/K164R double mutants, revealing an alternative TLS mechanism. REV1-/- and REV3L-/- mutants exhibit 500-5,000 bp deletions, and REV1-/- PRIMPOL-/- cells show chromosomal instability. TLS protects against deletions and large rearrangements but contributes to spontaneous base substitutions.
Article
Biochemistry & Molecular Biology
Hala Ouzon-Shubeita, Lillian F. Schmaltz, Seongmin Lee
Summary: MBD4 plays a crucial role in repairing and discriminating mismatched DNA, predominantly targeting methylated thymine and guanine bases. Arg468 and Lys are essential for MBD4 catalytic activity, facilitating the discrimination between substrate mismatches and nonsubstrate base pairs.
BIOCHEMICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Ilan Attali, Michael R. Botchan, James M. Berger
Summary: This article discusses recent progress in understanding the physical basis of replisome construction and progression in eukaryotes, highlighting the critical role played by large, dynamic protein-nucleic acid assemblies in this cellular process.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
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
Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Lyudmila Y. Kadyrova, You Jin Song, Qinyu Hao, Jaba Mitra, Rosaline Y. C. Hsu, Mariam K. Arif, Sneha Adusumilli, Ting-Wei Liao, Taekjip Ha, Farid A. Kadyrov, Kannanganattu V. Prasanth, Supriya G. Prasanth
Summary: This article investigates the role of Orc6, a component of the origin recognition complex (ORC), in DNA replication. The study discovers that Orc6 localizes at the replication fork and acts as an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during the S phase, Orc6 promotes MMR complex assembly and activity, enabling efficient MMR. This suggests that hOrc6 plays a fundamental role in genome surveillance during DNA replication.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Seijiro Shioi, Akiyoshi Shimamoto, Yingxia Song, Kyoko Hidaka, Maki Nakamura, Ayumi Take, Namiko Hayashi, Soichi Takiguchi, Ryosuke Fujikane, Masumi Hidaka, Shinya Oda, Yoshimichi Nakatsu
Summary: This study demonstrates that the Exo domain function of DNA polymerase delta plays a role in mononucleotide repeat stabilization in human cells, suggesting a potential division of roles between DNA polymerase and MMR in repeat maintenance in the human genome.
Article
Biochemistry & Molecular Biology
Yann Benureau, Caroline Pouvelle, Pauline Dupaigne, Sonia Baconnais, Eliana Moreira Tavares, Gerard Mazon, Emmanuelle Despras, Eric Le Cam, Patricia L. Kannouche
Summary: Research has found that DNA lesions in S phase can threaten genome stability, but specific damage tolerance mechanisms can overcome these obstacles and ensure the continuity of DNA synthesis. Specifically, the TLS polymerase eta plays a crucial role at the replication fork, and RAD51 also supports repriming at the replication fork, providing important clues for addressing issues caused by DNA damage.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mary E. Anderson, Janet L. Smith, Alan D. Grossman
Summary: DNA replication is regulated primarily at the initiation step, where DnaA and oriC are the key targets. Multiple mechanisms including elongation and initiation can compensate for over-initiation, highlighting the complexity of replication regulation.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sabrina X. Van Ravenstein, Kavi P. Mehta, Tamar Kavlashvili, Jo Ann W. Byl, Runxiang Zhao, Neil Osheroff, David Cortez, James M. Dewar
Summary: Using Xenopus egg extracts, this study demonstrates that the TOP2 poisons etoposide and doxorubicin inhibit DNA replication through different mechanisms. Etoposide induces TOP2-dependent DNA breaks and TOP2-dependent fork stalling, while doxorubicin stalls replication forks independently of TOP2 by intercalating into parental DNA.
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)