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Mre11–Rad50–Nbs1‐dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity
Author(s) -
Jazayeri Ali,
Balestrini Alessia,
Garner Elizabeth,
Haber James E,
Costanzo Vincenzo
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.128
Subject(s) - biology , rad50 , oligonucleotide , dna , computational biology , genetics , microbiology and biotechnology , dna binding protein , gene , transcription factor
DNA double‐strand breaks (DSBs) can be processed by the Mre11–Rad50–Nbs1 (MRN) complex, which is essential to promote ataxia telangiectasia‐mutated (ATM) activation. However, the molecular mechanisms linking MRN activity to ATM are not fully understood. Here, using Xenopus laevis egg extract we show that MRN‐dependent processing of DSBs leads to the accumulation of short single‐stranded DNA oligonucleotides (ssDNA oligos). The MRN complex isolated from the extract containing DSBs is bound to ssDNA oligos and stimulates ATM activity. Elimination of ssDNA oligos results in rapid extinction of ATM activity. Significantly, ssDNA oligos can be isolated from human cells damaged with ionizing radiation and injection of small synthetic ssDNA oligos into undamaged cells also induces ATM activation. These results suggest that MRN‐dependent generation of ssDNA oligos, which constitute a unique signal of ongoing DSB repair not encountered in normal DNA metabolism, stimulates ATM activity.