Article
Biochemistry & Molecular Biology
Robin Oz, Jing L. Wang, Raphael Guerois, Gaurav Goyal, Sriram Kk, Virginie Ropars, Rajhans Sharma, Firat Koca, Jean-Baptiste Charbonnier, Mauro Modesti, Terence R. Strick, Fredrik Westerlund
Summary: In this study, single-molecule techniques were used to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ). The findings suggest differences in the mechanisms of bacterial NHEJ compared to human NHEJ, with bacterial Ku playing a significant role in the process. The study also proposes evolutionary similarities between bacterial and eukaryotic NHEJ mechanisms.
NUCLEIC ACIDS 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
Plant Sciences
Hira Khan, Takashi Ochi
Summary: Non-homologous end joining (NHEJ) is important for repairing DNA double-strand breaks in plants, but the molecular mechanism of plant NHEJ is still unclear. This study discovered a previously unidentified plant ortholog of PAXX, which has a similar structure to human PAXX but functions similar to human XLF by interacting with Ku70/80 and XRCC4. This suggests that plant PAXX combines the roles of mammalian PAXX and XLF, indicating a functional redundancy between PAXX and XLF in plants.
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
Biochemistry & Molecular Biology
Benjamin M. Stinson, Joseph J. Loparo
Summary: DNA double-strand breaks are mainly repaired through nonhomologous end joining (NHEJ) in vertebrates, which requires efficient end synapsis and processing mechanisms to maintain genome stability.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Review
Genetics & Heredity
Dipayan Ghosh, Sathees C. Raghavan
Summary: This article discusses key proteins in the NHEJ repair pathway, such as PAXX, MRI/CYREN, TDP-43, IFFO1, ERCC6L2, and RNase H2, and their roles in the repair of double-strand breaks in the cell nucleus.
TRENDS IN GENETICS
(2021)
Article
Microbiology
Wen-Wei Zhang, Douglas G. Wright, Lynn Harrison, Greg Matlashewski
Summary: In this study, it was found that the protozoan parasite Leishmania lacks a functional NHEJ pathway but retains Ku70 and Ku80 proteins. Ku is involved in DSB repair and affects the repair outcome through different mechanisms. Additionally, Ku is required for the healthy growth of the parasite but is not important for maintaining telomere lengths.
Article
Biochemistry & Molecular Biology
Chuxuan Li, Hanwen Zhu, Shikai Jin, Leora M. Maksoud, Nikhil Jain, Ji Sun, Yang Gao
Summary: DNA polymerase theta (Pol theta) plays a crucial role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. This study presents cryo-electron microscope structures of Lates calcarifer Pol theta, revealing its interactions with long and short DNA substrates and its similarity to high-fidelity A-family polymerases. Computational simulations and mutagenesis studies suggest that unique insertion loops of Pol theta stabilize short DNA binding and assemble the active site for MMEJ repair. These findings provide a structural basis for understanding Pol theta-mediated MMEJ.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Suleman S. Hussain, Rahul Majumdar, Grace M. Moore, Himanshi Narang, Erika S. Buechelmaier, Maximilian J. Bazil, Pavithran T. Ravindran, Jonathan E. Leeman, Yi Li, Manisha Jalan, Kyrie S. Anderson, Andrea Farina, Rekha Soni, Neeman Mohibullah, Edin Hamzic, Xiaoqing Rong-Mullins, Christopher Sifuentes, Rama R. Damerla, Agnes Viale, Simon N. Powell, Daniel S. Higginson
Summary: This study developed a Cas9-based repair system with simplified repair outcomes and converted it into ddPCR readouts for easier use in more laboratories. The experiment found that the key Alt-EJ factor Pol theta only accounts for 50% of total Alt-EJ, SSTR requires BRCA1 and MRE11 activity, and BRCA1 promotes Alt-EJ usage at two-ended DSBs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Takashi Tsuyama, Kumiko Fujita, Ryosuke Sasaki, Shiori Hamanaka, Yuki Sotoyama, Akira Ogawa, Kana Kusuzaki, Yutaro Azuma, Shusuke Tada
Summary: RecQ4, a member of the RecQ helicase family, is involved in DNA double-strand break repair pathways NHEJ and HR. The N-terminal region N598 of Xenopus RecQ4 inhibits DNA end joining and affects the association of Ku70, potentially influencing the choice of DSB repair pathway.
Article
Biochemistry & Molecular Biology
Ujjayinee Ray, Vindya K. Gopinatha, Shivangi Sharma, Laijau Goyary, Bibha Choudhary, Kempegowda Mantelingu, Kanchugarakoppal S. Rangappa, Sathees C. Raghavan
Summary: The study describes the synthesis and characterization of several mercaptopyrimidine derivatives with potent anti-cancer properties. Particularly, compounds SCR116 and SCR132 showed increased cancer cell death and improved anti-cancer potential.
Article
Biochemistry & Molecular Biology
Dana J. Sowa, Monica M. Warner, Andriana Tetenych, Lucas Koechlin, Pardis Balari, Jose Pablo Rascon Perez, Cody Caba, Sara N. Andres
Summary: Bacterial non-homologous end joining requires the ligase LigD and Ku. The extended C-terminus of Ku restricts DNA binding, and certain amino acids in this region play a key role in this effect. While the minimal C-terminus is sufficient to stimulate double-stranded DNA ligation, the Ku core domain also contributes to this process. Additionally, both wildtype Ku and the Ku core domain alone directly bind to both the ligase and polymerase domains of LigD.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Genetics & Heredity
Christina A. Gerodimos, Go Watanabe, Michael R. Lieber
Summary: The nucleosomal state imposes strict constraints on NHEJ nuclease and ligase activities, and the presence of nucleosome-wrapped DNA ends can affect the joining process.
Article
Cell Biology
Crystal Lee, Jiyeon Leem, Jeong Su Oh
Summary: DNA double-strand breaks (DSBs) can cause genomic instability and are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR) pathways. However, their roles in oocyte meiotic maturation have not been well understood. This study shows that oocytes selectively use NHEJ and HR to repair DSBs during meiotic maturation, with NHEJ being critical for oocyte maturation with DNA damage and HR essential for maintaining centromere integrity.
CELL PROLIFERATION
(2023)
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)