Yeast XRS2 and human NBN gene: Experimental evidence for homology using codon optimized cDNA.

Autor: Demuth I; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Berlin, Germany.; Berlin-Brandenburg Center for Regenerative Medicine (BCRT), Charité University Medicine Berlin, Berlin, Germany., Krebs SK; Institute of Biotechnology, Technical University Berlin, Berlin, Germany., Dutrannoy V; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical and Human Genetics, Berlin, Germany., Linke C; Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany., Krobitsch S; Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany., Varon R; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical and Human Genetics, Berlin, Germany., Lang C; ORGANOBALANCE GmbH, Berlin, Germany., Raab A; ORGANOBALANCE GmbH, Berlin, Germany., Sperling K; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical and Human Genetics, Berlin, Germany., Digweed M; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical and Human Genetics, Berlin, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Nov 15; Vol. 13 (11), pp. e0207315. Date of Electronic Publication: 2018 Nov 15 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0207315
Abstrakt: The genes, XRS2 in Saccharomyces cerevisiae and NBN in mammals, have little sequence identity at the amino acid level. Nevertheless, they are both found together with MRE11 and RAD50 in a highly conserved protein complex which functions in the repair of DNA double-strand breaks. Here, we have examined the evolutionary and functional relationship of these two genes by cross-complementation experiments. These experiments necessitated sequence correction for specific codon usage before they could be successfully conducted. We present evidence that despite extreme sequence divergence nibrin can, at least partially, replace Xrs2 in the cellular DNA damage response, and Xrs2 is able to promote nuclear localization of MRE11 in NBS cells. We discuss that the extreme sequence divergence reflects a unique adaptive pressure during evolution related to the specific eukaryotic role for both Xrs2 and nibrin in the subcellular localisation of the DNA repair complex. This, we suggest, is of particular relevance when cells are infected by viruses. The conflict hypothesis of co-evolution of DNA repair genes and DNA viruses may thus explain the very low sequence identity of these two homologous genes.
Competing Interests: C.L. is the former director and now consultant of the ORGANOBALANCE GmbH, and A.R. is a former employee of this company. Through ORGANOBALANCE-affiliated coauthors, ORGANOBALANCE was involved in conceptualization of the study, project administration, review, and approval of the manuscript for publication and providing resources. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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