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Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks

Opened Access Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks

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Autor: Caron, Pierre
Choudjaye, Jonathan
Clouaire, Thomas
Bugler, Béatrix
Daburon, Virginie
Aguirrebengoa, Marion
Álvarez Quilón, Alejandro
Cortés Ledesma, Felipe
Fecha: 2015
Publicado en: Cell Reports, 13 (8), 1598-1609.
Tipo de documento: Artículo
Resumen: DNA double-strand breaks (DSBs) elicit the so-called DNA damage response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PKcs), two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains controversial. Using the DIvA system (DSB inducible via AsiSI) combined with high-resolution mapping and advanced microscopy, we uncovered that both ATM and DNA-PKcs spread in cis on a confined region surrounding DSBs, independently of the pathway used for repair. However, once recruited, these kinases exhibit non-overlapping functions on end joining and γH2AX domain establishment. More specifically, we found that ATM is required to ensure the association of multiple DSBs within “repair foci.” Our results suggest that ATM acts not only on chromatin marks but also on higher-order chromatin organization to ensure repair accuracy and survival.
Cita: Caron, P., Choudjaye, J., Clouaire, T., Bugler, B., Daburon, V., Aguirrebengoa, M.,...,Cortés Ledesma, F. (2015). Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks. Cell Reports, 13 (8), 1598-1609.
Tamaño: 2.959Mb
Formato: PDF

URI: http://hdl.handle.net/11441/63717

DOI: 10.1016/j.celrep.2015.10.024

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