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TIRR: a potential front runner in HDR race−hypotheses and perspectives

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Abstract

The majority of CRISPR-Cas9 methods for mutations correction are oriented on gene editing through homologous recombination that is normally restrained by non-homologous end joining (NHEJ). A recently identified protein TIRR can bind a 53BP1 protein, a key effector of NHEJ, and inhibit its recruitment to double-strand break loci. Several studies elucidated the molecular mechanisms of TIRR-53BP1 binding and established bidirectional role of TIRR in 53BP1 functions and stability. It was proved that overexpression of TIRR promotes the double-strand break repair through homologous recombination. All findings, which were described in the review, allow assuming TIRR as a suitable target for enhancing efficacy of genome editing through homology directed repair.

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Acknowledgements

The section “The interplay of the main factors managing repair of DNA DSB” was supported by the grant of the Russian Science Foundation (Agreement 17-75-20095), the section “The role of chromatin condition in the repair pathway choice” was supported by the Russian Academy of Sciences (Program “Fundamental researches for biomedical technologies”). The results of parts “The first histone-masking protein” and “TIRR role in DNA repair” were obtained within the state assignment of Ministry of Science and Higher Education of Russian Federation.

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  1. Laboratory of Genome Editing, Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moskvorechie, 1, Moscow, Russia, 115522

    A. A. Anuchina, A. V. Lavrov & S. A. Smirnikhina

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Anuchina, A.A., Lavrov, A.V. & Smirnikhina, S.A. TIRR: a potential front runner in HDR race−hypotheses and perspectives. Mol Biol Rep 47, 2371–2379 (2020). https://doi.org/10.1007/s11033-020-05285-x

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