Article
Multidisciplinary Sciences
Ke Zhang, Yang Sui, Wu-Long Li, Gen Chen, Xue-Chang Wu, Robert J. Kokoska, Thomas D. Petes, Dao-Qiong Zheng
Summary: The deficiency of Pol epsilon leads to genomic instability and multiple human diseases. Low levels of Pol epsilon result in cellular changes such as elevated rates of recombination, aneuploidy, contraction of ribosomal DNA repeats, shortened telomeres, increased break-induced replication, and higher rate of single-base mutations. Compared to other replicative DNA polymerases, Pol epsilon displays distinct patterns of genomic alterations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Gustavo Carvalho, Bruno Marcal Repoles, Isabela Mendes, Paulina H. Wanrooij
Summary: Research has focused on maintenance and instability of mitochondrial DNA, exploring the role of DNA repair factors in mitochondria and the connection between mtDNA damage and immune response. Future studies should delve into mechanisms by which mitochondria maintain mtDNA, the balance between repair and degradation, as well as the release of mtDNA into the cytosol.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Oncology
Akira Fujimori, Hirokazu Hirakawa, Cuihua Liu, Taishin Akiyama, Bevin P. Engelward, Jac A. Nickoloff, Masao Suzuki, Bing Wang, Mitsuru Nenoi, Sei Sai
Summary: This study aimed to investigate the role of homologous recombination (HR)-related genomic instability in ionizing radiation-induced thymic lymphoma in mice. The results showed that ionizing radiation induced genome instability, leading to the development of thymic lymphoma.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Review
Cell Biology
Shan Qiu, Guixing Jiang, Liping Cao, Jun Huang
Summary: Replication fork reversal is a critical protective mechanism in higher eukaryotic cells in response to replication stress, where forks change direction to form a Holliday junction-like structure for protection, with DNA damage repair proteins playing important roles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Jennifer A. Black, Joao Luis Reis-Cunha, Angela. K. Cruz, Luiz. R. O. Tosi
Summary: Leishmania is able to rapidly adjust gene expression by modifying gene copy number, using the products of genome instability. However, how Leishmania regulate genome plasticity to enhance fitness while avoiding toxic overexpression of co-amplified and co-transcribed genes remains unclear.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Genetics & Heredity
Justin A. Ling, Zach Frevert, M. Todd Washington
Summary: DNA damage can cause replication forks to stall, but cells have evolved translesion synthesis polymerases to incorporate nucleotides opposite DNA lesions. Recent methodological developments, including time-lapse X-ray crystallography, full-ensemble hybrid methods, and cryo-electron microscopy, have enhanced our understanding of the structures and mechanisms of these polymerases.
Article
Biochemistry & Molecular Biology
Almudena Serrano-Benitez, Sophie E. Wells, Lylah Drummond-Clarke, Lilian C. Russo, John Christopher Thomas, Giovanna A. Leal, Mark Farrow, James Michael Edgerton, Shankar Balasubramanian, Ming Yang, Christian Frezza, Amit Gautam, Jan Brazina, Kamila Burdova, Nicolas C. Hoch, Stephen P. Jackson, Keith W. Caldecott
Summary: DNA single-strand breaks (SSBs) play a role in disrupting DNA replication and causing chromosome breakage. This study investigates whether SSBs induce chromosome breakage when located behind or ahead of replication forks, and finds that only SSBs ahead of replication forks trigger fork collapse and chromosome breakage. Furthermore, the study shows that CldU, a thymidine analogue, is cytotoxic to cells lacking SSB repair mechanisms and its incorporation in template DNA is particularly harmful during the following cell cycle. Additionally, BRCA-defective cells are highly sensitive to CldU, suggesting its potential clinical utility.
Article
Multidisciplinary Sciences
Lea Marie, Lorraine S. Symington
Summary: This study reveals the recombination mechanism of repeated sequences under replication stress and proposes a model for generating chromosome rearrangements.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Hui Zhang
Summary: DNA replication licensing is tightly regulated in eukaryotic cells to ensure proper replication initiation and prevent re-replication, with key mechanisms involving degradation of Cdt1 protein by CRL4(Cdt2) ubiquitin E3 ligase. The interaction between Cdt1 and PCNA, facilitated by the PIP box domain, plays a crucial role in this process, highlighting the importance of regulating DNA replication and genome stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ziv Itzkovich, Karan Choudhary, Matan Arbel, Martin Kupiec
Summary: Timely and complete replication of the genome is crucial for life. The PCNA ring is essential for DNA replication and repair by enhancing the processivity of DNA polymerases and recruiting proteins involved in DNA replication-associated processes. The ELG1 gene encodes a protein that unloads PCNA from chromatin and its deletion results in genome instability, sensitivity to DNA damage, defects in genomic silencing, high mutation rates, and other significant phenotypes. This study demonstrates that the role of Elg1 in maintaining genome stability is primarily attributed to its effects on PCNA unloading, highlighting the importance of PCNA unloading for proper chromatin structure and genome stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Deon Ploessl, Yuxin Zhao, Mingfeng Cao, Saptarshi Ghosh, Carmen Lopez, Maryam Sayadi, Siva Chudalayandi, Andrew Severin, Lei Huang, Marissa Gustafson, Zengyi Shao
Summary: By developing a new CRISPR platform, the limitations caused by NHEJ repair have been successfully addressed, improving the accuracy of genome editing technology. While preserving NHEJ, it is also possible to effectively optimize microbial factories for the production of target compounds.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xian-Kun Tong, Heng Li, Li Yang, Shi-Zhe Xie, Sha Xie, Ying Gong, Cheng Peng, Xiao-Xiao Gao, Zheng-Li Shi, Xing-Lou Yang, Jian-Ping Zuo
Summary: To develop safe and innovative in vitro models for Ebola virus (EBOV) research, a recombinant Ebola virus was generated by replacing the glycoprotein (GP) gene with the Cre recombinase (Cre) gene using reverse genetics. This defective virus can multiply in a complementary permissive cell line and express GP and reporter protein in the presence of exogenous Cre. The model features intact viral life cycle, robust virus multiplication, normal virion morphology, and can be adapted for other viruses.
ANTIVIRAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yiwei He, Meghan V. Petrie, Haiyang Zhang, Jared M. Peace, Oscar M. Aparicio
Summary: Eukaryotic chromosomes have different replication timings, which are regulated by epigenetic mechanisms involving histone deacetylases. Histone deacetylase Sir2 negatively regulates replication initiation at multicopy rDNA origins, while Rpd3 histone deacetylase negatively regulates firing of single-copy origins. The effect of Rpd3 on single-copy origins may be indirect, mediated by its role in rDNA origin firing. Our experiments support the idea that origins compete for limiting factors, but Rpd3's effect on single-copy origins is independent of rDNA copy-number and Sir2's effects on rDNA origin firing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Anna S. Zhuk, Artem G. Lada, Youri I. Pavlov
Summary: Baker's yeast, S. cerevisiae, is widely used as a model organism for studying genome stability mechanisms. The genetic differences among commonly used yeast strains affect DNA replication, repair, and recombination processes. This study compared the genomic DNA sequence variation in five yeast strains used for studying these processes and found significant differences, even in closely related strains. These findings highlight the importance of considering strain polymorphisms when interpreting genome stability studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jelena Repar, Davor Zahradka, Ivan Sovic, Ksenija Zahradka
Summary: Genome stability in radioresistant bacterium Deinococcus radiodurans relies on RecA for repair of DNA double-strand breaks, with deletions in chromosome II being a common outcome in recA mutants. The mechanism behind these deletions involves short repeats and operates over larger linear DNA distances, resembling alternative end-joining. Despite different rearrangement patterns preselected in recA isolates, identified deletions overlap in a 35 kb genomic region, pointing towards a common underlying mechanism.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Hengyao Niu, Catherine J. Potenski, Anastasiya Epshtein, Patrick Sung, Hannah L. Klein
Editorial Material
Biochemistry & Molecular Biology
Sue Jinks-Robertson, Hannah L. klein
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Editorial Material
Biochemistry & Molecular Biology
Sue Jinks-Robertson, Hannah L. klein
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Sergio R. Santa Maria, YoungHo Kwon, Patrick Sung, Hannah L. Klein
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Multidisciplinary Sciences
Catherine J. Potenski, Hengyao Niu, Patrick Sung, Hannah L. Klein
Article
Biochemistry & Molecular Biology
Catherine J. Potenski, Hannah L. Klein
NUCLEIC ACIDS RESEARCH
(2014)
Article
Biochemistry & Molecular Biology
Andres Mansisidor, Temistocles Molinar, Priyanka Srivastava, Demetri D. Dartis, Adriana Pino Delgado, Hannah G. Blitzblau, Hannah Klein, Andreas Hochwagen
Editorial Material
Medicine, General & Internal
Hannah L. Klein, Lorraine S. Symington
NEW ENGLAND JOURNAL OF MEDICINE
(2019)
Editorial Material
Multidisciplinary Sciences
Hannah L. Klein
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Cell Biology
Hannah L. Klein, Kenny K. H. Ang, Michelle R. Arkin, Emily C. Beckwitt, Yi-Hsuan Chang, Jun Fan, Youngho Kwon, Michael J. Morten, Sucheta Mukherjee, Oliver J. Pambos, Hafez el Sayyed, Elizabeth S. Thrall, Joao P. Vieira-da-Rocha, Quan Wang, Shuang Wang, Hsin-Yi Yeh, Julie S. Biteen, Peter Chi, Wolf-Dietrich Heyer, Achillefs N. Kapanidis, Joseph J. Loparo, Terence R. Strick, Patrick Sung, Bennett Van Houten, Hengyao Niu, Eli Rothenberg
Article
Genetics & Heredity
Hannah L. Klein
Review
Biotechnology & Applied Microbiology
Hengyao Niu, Hannah L. Klein
FEMS YEAST RESEARCH
(2017)
Article
Cell Biology
Anastasiya Epshtein, Catherine J. Potenski, Hannah L. Klein
Review
Cell Biology
Hannah L. Klein, Giedre Bacinskaja, Jun Che, Anais Cheblal, Rajula Elango, Anastasiya Epshtein, Devon M. Fitzgerald, Belen Gomez-Gonzalez, Sharik R. Khan, Sandeep Kumar, Bryan A. Leland, Lea Marie, Qian Mei, Judith Mine-Hattab, Alicja Piotrowska, Erica J. Polleys, Christopher D. Putnam, Elina A. Radchenko, Anissia Ait Saada, Cynthia J. Sakofsky, Eun Yong Shim, Mathew Stracy, Jun Xia, Zhenxin Yan, Yi Yin, Andres Aguilera, Juan Lucas Argueso, Catherine H. Freudenreich, Susan M. Gasser, Dmitry A. Gordenin, James E. Haber, Grzegorz Ira, Sue Jinks-Robertson, Megan C. King, Richard D. Kolodner, Andrei Kuzminov, Sarah A. E. Lambert, Sang Eun Lee, Kyle M. Miller, Sergei M. Mirkin, Thomas D. Petes, Susan M. Rosenberg, Rodney Rothstein, Lorraine S. Symington, Pawel Zawadzki, Nayun Kim, Michael Lisby, Anna Malkova
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.