ATM specifically mediates repair of double-strand breaks with blocked DNA ends.

Abstract:

: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 signalling 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Álvarez-Quilón A,Serrano-Benítez A,Lieberman JA,Quintero C,Sánchez-Gutiérrez D,Escudero LM,Cortés-Ledesma F

doi

10.1038/ncomms4347

subject

Has Abstract

pub_date

2014-02-27 00:00:00

pages

3347

issn

2041-1723

pii

ncomms4347

journal_volume

5

pub_type

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