Background: The RAD21 cohesin plays, besides its well-recognised role in chromatid cohesion, a role in DNA double strand break (dsb) repair. In Arabidopsis there are three RAD21 paralog genes (AtRAD21.1, AtRAD21.2 and AtRAD21.3), yet only AtRAD21.1 has been shown to be required for DNA dsb damage repair. Further investigation of the role of cohesins in DNA dsb repair was carried out and is here reported.
Results: We show for the first time that not only AtRAD21.1 but also AtRAD21.3 play a role in somatic DNA dsb repair. Comet data shows that the lack of either cohesins induces a similar high basal level of DNA dsb in the nuclei and a slower DNA dsb repair kinetics in both cohesin mutants. The observed AtRAD21.3 transcriptional response to DNA dsb induction reinforces further the role of this cohesin in DNA dsb repair. The importance of AtRAD21.3 in DNA dsb damage repair, after exposure to DNA dsb damage inducing agents, is notorious and recognisably evident at the phenotypical level, particularly when the AtRAD21.1 gene is also disrupted.
Conclusions: Our data demonstrates that both Arabidopsis cohesin (AtRAD21.1 and AtRAD21.3) play a role in somatic DNA dsb repair. Furthermore, the phenotypical data from the atrad21.1 atrad21.3 double mutant indicates that these two cohesins function synergistically in DNA dsb repair. The implications of this data are discussed.
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http://dx.doi.org/10.1186/s12870-014-0353-9 | DOI Listing |
Radiat Res
December 2024
Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany.
It is thought that cells surviving ionizing radiation exposure repair DNA double-strand breaks (DSBs) and restore their genomes. However, the recent biochemical and genetic characterization of DSB repair pathways reveals that only homologous recombination (HR) can function in an error-free manner and that the non-homologous end joining (NHEJ) pathways canonical NHEJ (c-NHEJ), alternative end joining (alt-EJ), and single-strand annealing (SSA) are error-prone, and potentially leave behind genomic scars and altered genomes. The strong cell cycle restriction of HR to S/G2 phases and the unparalleled efficiency of c-NHEJ throughout the cell cycle, raise the intriguing question as to how far a surviving cell "reaches" after repairing the genome back to its pre-irradiation state.
View Article and Find Full Text PDFCurr Opin Pharmacol
December 2024
Biotechnology Research and Innovation Council - National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India; Biotechnology Research and Innovation Council - National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani 741251, India. Electronic address:
DNA damage signaling is a highly coordinated cellular process which is required for the removal of DNA lesions. Amongst the different types of DNA damage, double-strand breaks (DSBs) are the most harmful type of lesion that attenuates cellular proliferation. DSBs are repaired by two major pathways-homologous recombination (HR), and non-homologous end-joining (NHEJ) and in some cases by microhomology-mediated end-joining (MMEJ).
View Article and Find Full Text PDFiScience
December 2024
Division of Molecular Oncological Pharmacy, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
DNA double-strand breaks (DSBs) occurring within the genomic DNA of mammalian cells significantly impact cell survival, depending upon their repair capacity. This study presents a mathematical model to fit fibroblast survival rates with a sequence-specific DSB burden induced by the restriction enzyme AsiSI. When cells had a sporadic DSB burden under mixed culture, cell growth showed a good fit to the Lotka-Volterra competitive equation, predicting the presence of modifying factors acting as competitive cell-to-cell interactions compared to monocultures.
View Article and Find Full Text PDFThe Mre11 complex comprises Mre11, Rad50 and Nbs1 (Xrs2 in ). The core components, Mre11 and Rad50 are highly conserved, with readily identifiable orthologs in all clades of life, whereas Nbs1/Xrs2 are present only in eukaryotes. In eukaryotes, the complex is integral to the DNA damage response, acting in DNA double strand break (DSB) detection and repair, and the activation of DNA damage signaling.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Institute of Functional Genomics, Moscow State University, Moscow, 119991 Russia.
The CRISPR/Cas technology of targeted genome editing made it possible to carry out genetic engineering manipulations with eukaryotic genomes with a high efficiency. Targeted induction of site-specific DNA breaks is one of the key stages of the technology. The cell repairs the breaks via one of the two pathways, nonhomologous end joining (NHEJ) and homology-driven repair (HDR).
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