Review
Cell Biology
Stephanie M. Ackerson, Carlan Romney, P. Logan Schuck, Jason A. Stewart
Summary: Regulation of DNA double-strand breaks and telomeres in cells is diametrically opposed, with DSBs requiring quick recognition and repair while telomeres must be protected to prevent unwanted chromosome fusions. Decision on whether to join DNA ends is critical for genome stability, and processing of telomeres and DSBs share commonalities. Repair of DSBs is determined by decision points that shift towards homologous recombination (HR) or non-homologous end joining (NHEJ).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Bert van de Kooij, Haico van Attikum
Summary: The repair of DNA double-strand breaks plays a crucial role in maintaining genome integrity. Various pathways can repair the breaks, leading to either error-free or highly mutagenic outcomes. Genomic reporter constructs have been used extensively to study this process, allowing researchers to quantifiably assess repair by measuring the expression of fluorescent proteins. Recent advancements in genome editing technologies, such as CRISPR-Cas9, have further enhanced the utility of reporter constructs. In this review, the available DNA double-strand break repair pathway reporters will be discussed and compared, with considerations for choosing the appropriate reporter and future prospects in this field.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Nhung Pham, Zhenxin Yan, Yang Yu, Mosammat Faria Afreen, Anna Malkova, James E. Haber, Grzegorz Ira
Summary: The research demonstrates that mutagenic break-induced replication (BIR) is suppressed at two-ended DNA double-strand breaks (DSBs) by proteins coordinating the usage of two ends of a DSB. Key proteins involved in this suppression include ssDNA annealing proteins Rad52 and Rad59, D-loop unwinding helicase Mph1, and the Mre11-Rad50-Xrs2 complex promoting synchronous resection of DSB ends. Sir2 also plays a role in silencing heterochromatic repair templates to prevent BIR.
Article
Genetics & Heredity
Ian Yannuzzi, Margaret A. Butler, Joel Fernandez, Jeannine R. LaRocque
Summary: DNA double-strand breaks (DSBs) are a highly genotoxic form of DNA damage that can lead to chromosomal aberrations, making proper repair essential for maintaining genome integrity. DSBs can be repaired through non-homologous end joining (NHEJ) or homology-directed repair, both initiated by DNA end resection.
Article
Biochemistry & Molecular Biology
Cunliang Li, Yuyu Guo, Lili Wang, Shunping Yan
Summary: DNA double-strand breaks (DSBs) are highly toxic forms of DNA damage that pose a threat to genome stability. Homologous recombination is an error-free pathway for DSB repair, in which the evolutionarily conserved SMC5/6 complex plays crucial roles. It has been discovered that SMC5/6 recruits the PAF1 complex (PAF1C) to facilitate DSB repair in plants.
Article
Biochemistry & Molecular Biology
Ricardo Peraza-Vega, Mahara Valverde, Emilio Rojas
Summary: The repair of DNA damage is crucial for maintaining genetic information and cell functioning. Double-strand breaks (DSBs) are the most harmful type of DNA damage, and their repair involves two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). MiRNAs have been shown to play an important role in regulating genes involved in NHEJ and HRR, and alterations in miRNA expression can impact the ability of cells to repair DSBs and affect cancer therapy sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jenny Kaur Singh, Rebecca Smith, Magdalena B. Rother, Anton J. L. de Groot, Wouter W. Wiegant, Kees Vreeken, Ostiane D'Augustin, Robbert Q. Kim, Haibin Qian, Przemek M. Krawczyk, Roman Gonzalez-Prieto, Alfred C. O. Vertegaal, Meindert Lamers, Sebastien Huet, Haico van Attikum
Summary: The study reveals that PARP1-driven chromatin expansion facilitates the recruitment of ZNF384, which subsequently recruits Ku70/Ku80 to promote cNHEJ. This plays a crucial role in repairing DSBs and maintaining genome stability.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Xiaoqing Fan, Suling Sun, Haoran Yang, Huihui Ma, Chenggang Zhao, Wanxiang Niu, Junqi Fan, Zhiyou Fang, Xueran Chen
Summary: This study reveals the inactivation of the ZDHHC16/SETD2/H3K36me3 signaling axis in EGFR-altered GBM, which affects DNA damage repair signaling. The depalmitoylation inhibitor, PalmB, shows potential as a novel adjuvant treatment for GBM patients undergoing radiation therapy.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Oncology
Zhen Qian, Nannan Feng, Anke Geng
Summary: Hepatocellular carcinoma (HCC) is a common malignant tumor with increasing incidence and high mortality rates. This study found that the compound tanshinone I inhibited the proliferation of HCC cells in a dose-dependent manner. It was also observed that tanshinone I disrupted genome stability by inhibiting DNA double strand break repair pathways. Importantly, combining tanshinone I with radiotherapy showed better therapeutic potential for treating HCC.
CANCER BIOLOGY & THERAPY
(2023)
Article
Multidisciplinary Sciences
Rajashree A. Deshpande, Alberto Marin-Gonzalez, Hannah K. Barnes, Phillip R. Woolley, Taekjip Ha, Tanya T. Paull
Summary: The MRN complex recognizes and processes DNA double-strand breaks by performing short-range removal of 5' strands, requiring stable binding of DNA-PK. Intermediates are efficiently generated within 200 bp of break site when DNA-PK is catalytically blocked. Results suggest a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.
NATURE COMMUNICATIONS
(2023)
Review
Genetics & Heredity
Atsushi Shibata, Penny A. Jeggo
Summary: ATM is a central kinase that activates a wide range of responses to cellular stress through signaling. It plays multiple roles in response to DNA damage, particularly focusing on DSB repair. Dysfunction in stress responses impairs repair accuracy, leading to dramatic sensitivity to ionizing radiation in ataxia telangiectasia (A-T) cells.
Review
Genetics & Heredity
Alice Libri, Timea Marton, Ludovic Deriano
Summary: DNA double-strand breaks are highly toxic and can be repaired via multiple DNA repair pathways. During V(D)J recombination, certain parameters restrict the repair of DSBs to the non-homologous end-joining pathway.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Aleksandar Zdravkovic, James M. Daley, Arijit Dutta, Tatsuya Niwa, Yasuto Murayama, Shuji Kanamaru, Kentaro Ito, Takahisa Maki, Bilge Argunhan, Masayuki Takahashi, Hideo Tsubouchi, Patrick Sung, Hiroshi Iwasaki
Summary: The Mre11-Rad50-Nbs1 complex is critical for repairing DNA double-strand breaks through homologous recombination, with its endonuclease activity being stimulated by Ctp1 phosphorylation. The recruitment of the highly conserved extreme C terminus of Ctp1 plays a pivotal role in the activation of the Mre11 endonuclease. This stimulatory mechanism appears to be generalizable to the human CtIP equivalent, suggesting an evolutionary conservation of this function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Daipayan Banerjee, Kurt Langberg, Salar Abbas, Eric Odermatt, Praveen Yerramothu, Martin Volaric, Matthew A. Reidenbach, Kathy J. Krentz, C. Dustin Rubinstein, David L. Brautigan, Tarek Abbas, Bradley D. Gelfand, Jayakrishna Ambati, Nagaraj Kerur
Summary: cGAMP, in addition to activating interferon pathways for protection against pathogens, also activates DNA damage response signaling and suppresses homology-directed repair.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Maria Sadek, Anand Sheth, Grant Zimmerman, Emily Hays, Renier Velez-Cruz
Summary: SWI/SNF complexes, frequently mutated in human cancers, not only regulate transcription but also play a role in the repair of DNA double strand breaks (DSBs). This discovery reveals a potential therapeutic target for SWI/SNF-mutated cancers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
C. Chalermrujinanant, W. Michowski, G. Sittithumcharee, F. Esashi, S. Jirawatnotai
Article
Oncology
Ying Shen, Jie Li, Masayuki Nitta, Diahnn Futalan, Tyler Steed, Jeffrey M. Treiber, Zack Taich, Deanna Stevens, Jill Wykosky, Hong-Zhuan Chen, Bob S. Carter, Oren J. Becher, Richard Kennedy, Fumiko Esashi, Jann N. Sarkaria, Frank B. Furnari, Webster K. Cavenee, Arshad Desai, Clark C. Chen
Article
Cell Biology
Pavel Moudry, Kenji Watanabe, Kamila M. Wolanin, Jirina Bartkova, Isabel E. Wassing, Sugiko Watanabe, Robert Strauss, Rune Troelsgaard Pedersen, Vibe H. Oestergaard, Michael Lisby, Miguel Andujar-Sanchez, Apolinar Maya-Mendoza, Fumiko Esashi, Jiri Lukas, Jiri Bartek
JOURNAL OF CELL BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Marjorie Fournier, Meritxell Orpinell, Cedric Grauffel, Elisabeth Scheer, Jean-Marie Garnier, Tao Ye, Virginie Chavant, Mathilde Joint, Fumiko Esashi, Annick Dejaegere, Pierre Gonczy, Laszlo Tora
NATURE COMMUNICATIONS
(2016)
Article
Multidisciplinary Sciences
Jean-Yves Bleuyard, Marjorie Fournier, Ryuichiro Nakato, Anthony M. Couturier, Yuki Katou, Christine Ralf, Svenja S. Hester, Daniel Dominguez, Daniela Rhodes, Timothy C. Humphrey, Katsuhiko Shirahige, Fumiko Esashi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Biochemistry & Molecular Biology
Jean-Yves Bleuyard, Remi Buisson, Jean-Yves Masson, Fumiko Esashi
Article
Oncology
Kunal A. Lodhia, Shan Gao, Tamara Aleksic, Fumiko Esashi, Valentine M. Macaulay
INTERNATIONAL JOURNAL OF CANCER
(2015)
Article
Biochemistry & Molecular Biology
Keiko Yata, Janette Lloyd, Sarah Maslen, Jean-Yves Bleuyard, Mark Skehel, Stephen J. Smerdon, Fumiko Esashi
Article
Cell Biology
Dafni-Eleftheria Pefani, Robert Latusek, Isabel Pires, Anna M. Grawenda, Karen S. Yee, Garth Hamilton, Louise van der Weyden, Fumiko Esashi, Ester M. Hammond, Eric O'Neill
NATURE CELL BIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Maurizio Mauro, Meghan A. Rego, Rebecca A. Boisvert, Fumiko Esashi, Francesca Cavallo, Maria Jasin, Niall G. Howlett
NUCLEIC ACIDS RESEARCH
(2012)
Article
Cell Biology
Keiko Yata, Jean-Yves Bleuyard, Ryuichiro Nakato, Christine Ralf, Yuki Katou, Rebekka A. Schwab, Wojciech Niedzwiedz, Katsuhiko Shirahige, Fumiko Esashi
Article
Biochemistry & Molecular Biology
Federico Paoletti, Afaf H. El-Sagheer, Jun Allard, Tom Brown, Omer Dushek, Fumiko Esashi
Review
Biochemistry & Molecular Biology
Xanita Saayman, Fumiko Esashi
Summary: DNA double-strand breaks can be toxic to the human genome and lead to premature aging, neurodegenerative disorders, and carcinogenesis. Recent advancements in sequencing technologies allow the systematic mapping of genome instability hotspots. These breakomes challenge the traditional paradigm of DNA breakage primarily occurring in hard-to-replicate regions and provide insights into biological mechanisms related to genome instability.
Article
Multidisciplinary Sciences
Isabel E. Wassing, Emily Graham, Xanita Saayman, Lucia Rampazzo, Christine Ralf, Andrew Bassett, Fumiko Esashi
Summary: The study reveals a previously unknown function of RAD51 in promoting genomic stability during mitosis by protecting under-replicated DNA, promoting mitotic DNA synthesis (MiDAS), and successful chromosome segregation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Xanita Saayman, Emily Graham, Chin Wei Brian Leung, Fumiko Esashi
Summary: In this study, a new protocol called exo-FISH is presented for labeling exposed single-stranded DNA in defined repetitive regions of mammalian genomes. This is achieved by combining in vitro restriction enzyme digestion on fixed cells with fluorescence in situ hybridization (FISH). The article describes the steps for cell harvesting and fixation, slide treatments, FISH probe hybridization, as well as imaging and analysis procedures.
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.
