Referencia

NatCommun. 2014; 5:3347. doi: 10.1038/ncomms4347

Autores

Alejandro Álvarez-Quilón, Almudena Serrano-Benítez, Jenna Ariel Lieberman, Cristina Quintero, Daniel Sánchez-Gutiérrez, Luis M. Escudero, Felipe Cortés-Ledesma

Resumen

Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signaling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked. We therefore identify the nature of ATM involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic trigger of ataxia telangiectasia and related disorders.

Descripción

La Ataxia telangiectasia esta causada por mutaciones en ATMy representa un paradigma para la predisposición a cáncer y síndromes neurodegenerativos ligados a defectos en la reparación de daño en el ADN. Nuestro trabajo identifica a ATM como factor esencial en la reparación de roturas de doble cadena bloqueadas, proponiéndolas como posible causa subyacente a la enfermedad Ataxia telangiectasia y a síndromes relacionados.

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

La reparación de roturas en el ADN es esencial para el normal desarrollo y mantenimiento de los sistemas inmune y nervioso, así como para evitar procesos tumorales. Consecuentemente, la pérdida de función de componentes de esta maquinaria se encuentra asociada a síndromes genéticos humanos caracterizados por problemas neurológicos y/o inmunológicos, que pueden además conllevar un aumento en la incidencia de cáncer. Por otro lado, la mayor parte de los tratamientos del cáncer empleados en la actualidad incluyen agentes que inducen roturas en el ADN. En el laboratorio del Dr. Cortés-Ledesma estudiamos los mecanismos moleculares implicados en la reparación de roturas en el ADN, así como las consecuencias fisiológicas que éstos pueden tener en el contexto de la salud humana.

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