Mgm101: A double-duty Rad52-like protein |
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Authors: | Jana Rendeková Thomas A. Ward Lucia Šimoničová Peter H. Thomas Jozef Nosek Ľubomír Tomáška |
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Affiliation: | 1. Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Science, Bratislava, Slovak Republic;2. Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK;3. Department of Genetics, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia;4. Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia |
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Abstract: | Mgm101 has well-characterized activity for the repair and replication of the mitochondrial genome. Recent work has demonstrated a further role for Mgm101 in nuclear DNA metabolism, contributing to an S-phase specific DNA interstrand cross-link repair pathway that acts redundantly with a pathway controlled by Pso2 exonuclease. Due to involvement of FANCM, FANCJ and FANCP homologues (Mph1, Chl1 and Slx4), this pathway has been described as a Fanconi anemia-like pathway. In this pathway, Mgm101 physically interacts with the DNA helicase Mph1 and the MutSα (Msh2/Msh6) heterodimer, but its precise role is yet to be elucidated. Data presented here suggests that Mgm101 functionally overlaps with Rad52, supporting previous suggestions that, based on protein structure and biochemical properties, Mgm101 and Rad52 belong to a family of proteins with similar function. In addition, our data shows that this overlap extends to the function of both proteins at telomeres, where Mgm101 is required for telomere elongation during chromosome replication in rad52 defective cells. We hypothesize that Mgm101 could, in Rad52-like manner, preferentially bind single-stranded DNAs (such as at stalled replication forks, broken chromosomes and natural chromosome ends), stabilize them and mediate single-strand annealing-like homologous recombination event to prevent them from converting into toxic structures. |
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Keywords: | DNA interstrand cross-link repair Fanconi anemia Mgm101 mitochondrial DNA Rad52 telomere yeast |
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