Article
Multidisciplinary Sciences
Jessica S. Williams, Percy P. Tumbale, Mercedes E. Arana, Julian A. Rana, R. Scott Williams, Thomas A. Kunkel
Summary: DNA ligase 1 finalizes eukaryotic nuclear DNA replication by sealing Okazaki fragments using DNA end-joining reactions, and high-fidelity DNA ligation is crucial for preventing accumulation of insertion mutations in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Claire Chung, Bert M. Verheijen, Zoe Navapanich, Eric G. McGann, Sarah Shemtov, Guan-Ju Lai, Payal Arora, Atif Towheed, Suraiya Haroon, Agnes Holczbauer, Sharon Chang, Zarko Manojlovic, Stephen Simpson, Kelley W. Thomas, Craig Kaplan, Peter van Hasselt, Marc Timmers, Dorothy Erie, Lin Chen, Jean-Francois Gout, Marc Vermulst
Summary: Accurate transcription is crucial for the faithful expression of genetic information. This study measured the error rate of transcription in five organisms and found variations in RNA polymerase II error rates among species. The research also identified genetic factors that affect transcription fidelity and provided insights into the co-evolution of transcription error rate and the genetic code.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Scott Alexander Lujan, Thomas A. Kunkel
Summary: This study describes the contribution of DNA mismatch repair (MMR) to the stability of the eukaryotic nuclear genome determined by whole-genome sequencing. While mutation rates in wild-type nuclear genomes are known for over 40 eukaryotic species, fewer measurements have been done in mismatch repair-defective organisms, mainly focusing on Saccharomyces cerevisiae and human tumors. Well-studied organisms include Drosophila melanogaster and Mus musculus, while less genetically tractable species include great apes and long-lived trees. Various techniques have been developed to gather mutation rates per generation or per cell division, and mechanistic studies involving genetic manipulation of MMR genes have been limited to specific organisms like yeast, Arabidopsis thaliana, Caenorhabditis elegans, and one chicken cell line. The few MMR studies reported to date indicate a significant contribution of MMR to genome stability, providing insights that would have been impossible to obtain through reporter gene assays.
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
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
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
Chemistry, Multidisciplinary
Xue Dong, Pei Pan, Qiu-Ling Zhang, Jing-Jie Ye, Peng Bao, Xuan Zeng, Xian-Zheng Zhang
Summary: This study developed a magnetic nanoparticle-mediated CRISPR/Cas9 system to target and inactivate the Mlh1 gene, resulting in enhanced tumor immunogenicity. In vitro and in vivo experiments demonstrated that this strategy effectively suppressed tumor growth and improved infiltration of CD8(+) T cells and response to immune checkpoint blockade therapy.
Article
Biochemistry & Molecular Biology
Xingyu Yin, Horia Popa, Anthony Stapon, Emilie Bouda, Miguel Garcia-Diaz
Summary: Genomic variations in SARS-CoV-2 have led to the emergence of more infectious variants. The replication fidelity of the virus is greatly affected when lacking the proofreading subunit, resulting in lower accuracy. Mutations in the nsp12 and nsp14 genes are likely to reduce replication fidelity, providing insight for future antiviral drugs and vaccine development.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Oncology
Hong Yuan, Jun Ji, Min Shi, Yan Shi, Jing Liu, Junwei Wu, Chen Yang, Wenqi Xi, Qingyuan Li, Wei Zhu, Jingjie Li, Xiaoli Gong, Jun Zhang
Summary: This study characterized hypermutated tumors and demonstrated that DNA damage repair plays a critical role in hypermutation based on the analysis of 5,980 tumor samples. High mutation rates were detected in DNA mismatch repair genes and polymerase genes in the hypermutated group, along with overlap between high TMB, high microsatellite instability, and high PD-L1. Mutant genes like EGFR, KRAS, and PIK3CA were found to be enriched in oncogenic signaling and DNA damage repair pathways. The study also highlighted significant differences in somatic cell characteristics and distribution between hypermutated and non-hypermutated groups.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Martina Fiumara, Samuele Ferrari, Attya Omer-Javed, Stefano Beretta, Luisa Albano, Daniele Canarutto, Angelica Varesi, Chiara Gaddoni, Chiara Brombin, Federica Cugnata, Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Bernhard Gentner, Ivan Merelli, Luigi Naldini
Summary: Base and prime editors have shown potential for precise genetic engineering, but their cellular responses and genotoxicity are not well understood. This study compared the efficiency, toxicity, and genotoxicity between base and prime editors and Cas9 in human hematopoietic cells. The findings suggest that these editors can induce harmful effects and genotoxicity, raising concerns for their clinical applications.
NATURE BIOTECHNOLOGY
(2023)
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
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.
Article
Oncology
Christopher J. Schwartz, Edaise M. da Silva, Antonio Marra, Andrea M. Gazzo, Pier Selenica, Vikas K. Rai, Diana Mandelker, Fresia Pareja, Maksym Misyura, Timothy M. D'Alfonso, Edi Brogi, Pamela Drullinsky, Pedram Razavi, Mark E. Robson, Joshua Z. Drago, Hannah Y. Wen, Liying Zhang, Britta Weigelt, Jinru Shia, Jorge S. Reis-Filho, Hong Zhang
Summary: A subset of breast cancers developing in individuals with Lynch syndrome are etiologically linked to MMR deficiency and may benefit from anti-PD1/PD-L1 immunotherapy.
CLINICAL CANCER RESEARCH
(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
Oncology
Emily N. Risdon, Cindy H. Chau, Douglas K. Price, Oliver Sartor, William D. Figg
Summary: The U.S. FDA approved two PARP inhibitors, olaparib and rucaparib, for treating metastatic castrate resistant prostate cancer with biomarker-positive patients. The benefits of PARP inhibition have been well studied in patients with BRCA1 and BRCA2 mutations, and there is potential to expand the use of PARP inhibitors to mutations in other non-BRCA DNA damage repair genes, increasing the patient population that could benefit from this treatment. Understanding the significance of PARP inhibitor-sensitizing alterations in other common non-BRCA DDR genes will help guide clinical decisions to offer targeted treatment options to a wider population of patients.
Article
Genetics & Heredity
Brittany A. Niccum, Heewook Lee, Wazim MohammedIsmail, Haixu Tang, Patricia L. Foster
Article
Microbiology
Lacey L. Westphal, Jasmine Lau, Zuly Negro, Ivan J. Moreno, Wazim Ismail Mohammed, Heewook Lee, Haixu Tang, Steven E. Finkel, Karin E. Kram
RESEARCH IN MICROBIOLOGY
(2018)
Article
Genetics & Heredity
Patricia L. Foster, Brittany A. Niccum, Ellen Popodi, Jesse P. Townes, Heewook Lee, Wazim MohammedIsmail, Haixu Tang
Article
Biochemistry & Molecular Biology
Xiaoqian Jiang, Haixu Tang, Wazim Mohammed Ismail, Michael Lynch
MOLECULAR BIOLOGY AND EVOLUTION
(2018)
Article
Microbiology
Brittany A. Niccum, Heewook Lee, Wazim MohammedIsmail, Haixu Tang, Patricia L. Foster
Article
Biotechnology & Applied Microbiology
Wazim Mohammed Ismail, Haixu Tang
Article
Genetics & Heredity
Brittany A. Niccum, Christopher P. Coplen, Heewook Lee, Wazim Mohammed Ismail, Haixu Tang, Patricia L. Foster
Meeting Abstract
Hematology
Terra Lasho, Christy Finke, Michael M. Timm, Robert Durruthy-Durruthy, Marc Arribas-Layton, Mrinal M. Patnaik, Ayalew Tefferi, Naseema Gangat, Abhishek A. Mangaonkar, Moritz Binder, Alexandre Gaspar Maia, Wazim Mohammed Ismail, Matthew T. Howard, Nicholas Chia
Meeting Abstract
Hematology
Marissa Li, Terra Lasho, Moritz Binder, Wazim Mohammed Ismail, Susan M. Geyer, Jenna Fernandez, Yael Kusne, Abhishek A. Mangaonkar, Minsuk Kim, Alexandre Gaspar Maia, Nicholas Chia, Mrinal M. Patnaik
Article
Microbiology
Patricia L. Foster, Brittany A. Niccum, Heewook Lee
Summary: Encounters between DNA replication and transcription may lead to genomic disruption, but whether this contributes to mutations is debated. This study found that in mismatch repair-defective E. coli, there were no significant differences in mutation frequencies between genes oriented codirectionally and those oriented head-on to replication. Biases in mutation frequencies among highly expressed genes were mainly due to the positions of tRNA genes containing mononucleotide runs.
Article
Biology
Wazim Mohammed Ismail, Amelia Mazzone, Flavia G. Ghiraldini, Jagneet Kaur, Manvir Bains, Amik Munankarmy, Monique S. Bagwell, Stephanie L. Safgren, John Moore-Weiss, Marina Buciuc, Lynzie Shimp, Kelsey A. Leach, Luis F. Duarte, Chandandeep S. Nagi, Saul Carcamo, Chi-Yeh Chung, Dan Hasson, Neda Dadgar, Jian Zhong, Jeong-Heon Lee, Fergus J. Couch, Alexander Revzin, Tamas Ordog, Emily Bernstein, Alexandre Gaspar-Maia
Summary: MacroH2A histone variants mark a subset of enhancers in normal and cancer cells, termed "macro-Bound Enhancers", which modulate enhancer activity. They are localized at enhancer elements lacking H3K27ac in a cell type-specific manner, maintaining cell identity. In breast cancer, reactivation of macro-bound enhancers is associated with oncogenic programs, while their repressive role is linked to macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Additionally, macroH2A deficiency enhances the activity of transcription factors associated with stem cell activity in normal mammary stem cells.
COMMUNICATIONS BIOLOGY
(2023)
Review
Mathematical & Computational Biology
Wazim Mohammed Ismail, Etienne Nzabarushimana, Haixu Tang
QUANTITATIVE BIOLOGY
(2019)