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Polμ tumor variants decrease the efficiency and accuracy of NHEJ

Opened Access Polμ tumor variants decrease the efficiency and accuracy of NHEJ


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Autor: Sastre Moreno, Guillermo
Pryor, John M.
Díaz Talavera, Alberto
Ruiz Pérez, José Francisco
Ramsden, Dale A.
Blanco, Luis
Departamento: Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
Fecha: 2017
Publicado en: Nucleic Acids Research, 45 (17), 10018-10031.
Tipo de documento: Artículo
Resumen: The non homologous end-joining (NHEJ) pathway of double-strand break (DSB) repair often requires DNA synthesis to fill the gaps generated upon alignment of the broken ends, a complex task performed in human cells by two specialized DNA polymerases, Polλ and Polμ. It is now well established that Polμ is the one adapted to repair DSBs with non-complementary ends, the most challenging scenario, although the structural basis and physiological implications of this adaptation are not fully understood. Here, we demonstrate that two human Polμ point mutations, G174S and R175H, previously identified in two different tumor samples and affecting two adjacent residues, limit the efficiency of accurate NHEJ by Polμ in vitro and in vivo. Moreover, we show that this limitation is the consequence of a decreased template dependency during NHEJ, which renders the error-rate of the mutants higher due to the ability of Polμ to randomly incorporate nucleotides at DSBs. These results highlight the relevanc...
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Cita: Sastre Moreno, G., Pryor, J.M., Díaz Talavera, A., Ruiz Pérez, J.F., Ramsden, D.A. y Blanco, L. (2017). Polμ tumor variants decrease the efficiency and accuracy of NHEJ. Nucleic Acids Research, 45 (17), 10018-10031.
Tamaño: 5.340Mb
Formato: PDF


DOI: 10.1093/nar/gkx625

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