Article
Biochemistry & Molecular Biology
Helene Bordelet, Rafael Costa, Clementine Brocas, Jordane Depagne, Xavier Veaute, Didier Busso, Amandine Batte, Raphael Guerois, Stephane Marcand, Karine Dubrana
Summary: Heterochromatin proteins, particularly the SIR complex, play a crucial role in regulating DNA repair pathways in yeast, with a focus on NHEJ. Sir3 interacts with the Sae2 protein to impair MRX complex functions, ultimately promoting NHEJ by limiting DNA resection and delaying MRX removal from DSB ends.
Review
Biochemistry & Molecular Biology
Richard L. Frock, Cheyenne Sadeghi, Jodie Meng, Jing L. Wang
Summary: Humans have evolved multiple DNA double-strand break repair pathways, with NHEJ and A-EJ functioning in different cell cycle phases. While NHEJ is primarily utilized for covalent rejoining of DNA ends, A-EJ can also repair DSBs in the absence of NHEJ.
Article
Microbiology
Jillian Romsdahl, Zachary Schultzhaus, Amy Chen, Jing Liu, Alexander Ewing, Judson Hervey, Zheng Wang
Summary: Fungi exhibit resistance to high levels of ionizing radiation, which can be increased through adaptive laboratory evolution. By using black yeast Exophiala dermatitidis, researchers demonstrated that gamma-radiation resistance can be greatly enhanced through repeated rounds of irradiation and outgrowth, leading to the identification of genetic mutations associated with ionizing radiation resistance. Disruption of the non-homologous end-joining pathway was found to greatly increase resistance to gamma-radiation in E. dermatitidis, suggesting the importance of homologous and non-homologous repair pathways in fungal radiation resistance.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Biology
Simon Magin, Prabodha Kumar Meher, George Iliakis
Summary: Alt-EJ is a DNA repair pathway that can be utilized by vertebrate cells to repair DNA double-strand breaks, but its engagement is linked to genomic instability. Exposure to ionizing radiation and treatment with nucleoside analogs can sensitize cells to radiation by increasing alt-EJ engagement and suppressing homologous recombination. This pathway shift may reflect a compensatory response to HR suppression in S and G2 phase cells.
RADIATION RESEARCH
(2021)
Article
Plant Sciences
Fabienne Gehrke, Angelina Schindele, Holger Puchta
Summary: Heritable plant chromosome engineering can be achieved in somatic cells using CRISPR/Cas to induce nonhomologous double-strand break repair pathways. This technology allows for large-scale restructuring of plant chromosomes, including duplications, inversions, and translocations. The use of nonhomologous end joining pathways in somatic cells facilitates efficient chromosomal rearrangements. This breakthrough has the potential to revolutionize plant breeding.
Article
Cell Biology
Marta Llorens-Agost, Michael Ensminger, Hang Phuong Le, Anugrah Gawai, Jie Liu, Andres Cruz-Garcia, Sarita Bhetawal, Richard D. Wood, Wolf-Dietrich Heyer, Markus Loebrich
Summary: BRCA2-deficient cells are vulnerable to inactivation of DNA repair pathways for DSBs, which can be exploited clinically. RAD52 and BRCA2 regulate the TMEJ process by blocking the POL theta function, ensuring proper repair of DSBs in mitosis.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jae Jin Kim, Seo Yun Lee, Yiseul Hwang, Soyeon Kim, Jee Min Chung, Sangwook Park, Junghyun Yoon, Hansol Yun, Jae-Hoon Ji, Sunyoung Chae, Hyeseong Cho, Chan Gil Kim, Ted M. Dawson, Hongtae Kim, Valina L. Dawson, Ho Chul Kang
Summary: Mutual crosstalk among PAR, PARP1 metabolites, and DNA repair machinery is a key regulatory mechanism of DDR. USP39, identified as an inactive DUB associated with PAR-coupled DDR, localizes to DNA lesions in a PAR-dependent manner, regulating NHEJ and liquid demixing. Additionally, the USP39-associated spliceosome complex controls homologous recombination repair in a PAR-independent manner.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Raquel Gago-Fuentes, Valentyn Oksenych
Summary: NHEJ factors XLF, DNA-PKcs, and PAXX play crucial roles in maintaining neural stem and progenitor cell populations and neurodevelopment in mammals, particularly evident in double knockout models.
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)
Review
Cell Biology
Dale A. Ramsden, Juan Carvajal-Garcia, Gaorav P. Gupta
Summary: DNA polymerase theta (Pol theta)-mediated end joining is a recently characterized DNA repair pathway that functions in various cellular contexts to repair DNA double-strand breaks that are not repaired by other pathways. Pol theta-mediated end joining both helps maintain the genome and causes genome instability, and is an emerging therapeutic target in cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Review
Oncology
Jacqueline A. Brinkman, Yue Liu, Stephen J. Kron
Summary: This article discusses the role of genotoxic therapy in cancer treatment and explores the potential of repurposing existing drugs and compounds as chemo or radiosensitizers. By studying cellular mechanisms as a framework, identifying which drugs and natural products have the most potential for repurposing is highlighted. The crucial next step is to conduct clinical trials to translate laboratory discoveries into benefiting patients.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Oncology
Daniele Caracciolo, Caterina Riillo, Maria Teresa Di Martino, Pierosandro Tagliaferri, Pierfrancesco Tassone
Summary: Cancer onset and progression result in high levels of DNA damage, with error-prone DNA repair pathways promoting genomic instability that leads to the appearance of cancer hallmarks through progressive genetic aberrations in tumor cells. This provides a potential target for precision oncology through the inhibition of Alternative Non-Homologous End Joining (Alt-NHEJ) as a new cancer vulnerability.
Review
Plant Sciences
Jason Sims, Fernando A. Rabanal, Christiane Elgert, Arndt Von Haeseler, Peter Schloegelhofer
Summary: Ribosomal RNA genes are organized in large domains of hundreds of rDNA units, with stable inheritance crucial for survival. During meiosis, rDNA loci are embedded within the nucleolus favoring non-homologous end joining as a repair mechanism, while rare homologous recombination events dynamically change rDNA unit numbers. The sequence heterogeneity and size stability of rDNA clusters in Arabidopsis thaliana show potential functional implications and drive further research into the mechanisms maintaining their metastable state.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Biotechnology & Applied Microbiology
Wenxin Bai, Meilan Huang, Chun Li, Jun Li
Summary: In this article, we comprehensively reviewed the recent industrial applications of yeast cell factories' genome editing systems. By using CRISPR-mediated genome editing systems, mutations can be introduced by artificially creating double-strand breaks (DSBs) and repaired with the assistance of intracellular DSB repair. We discussed various strategies of DSB repair and gene editing efficiencies, and provided a direction for further development of yeast genome editing.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaolu Ma, Chen Wang, Bo Zhou, Zina Cheng, Zhiyong Mao, Tie-Shan Tang, Caixia Guo
Summary: This study demonstrated the important role of Pol eta in ETO-induced DSB repair, and identified Kap1 as a novel regulator. Kap1 regulates the function of Pol eta in DSB repair by facilitating Rad18 recruitment and stabilizing the Rad18-Pol eta association.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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.