[No authors listed]
The Mre11-Rad50-Nbs1 (MRN) protein complex and ATM/Tel1 kinase protect genome integrity through their functions in DNA double-strand break (DSB) repair, checkpoint signaling, and telomere maintenance. Nbs1 has a conserved C-terminal motif that binds ATM/Tel1, but the full extent and significance of ATM/Tel1 interactions with MRN are unknown. Here, we show that Tel1 overexpression bypasses the requirement for Nbs1 in DNA damage signaling and telomere maintenance. These activities require Mre11-Rad50, which localizes to DSBs and bind Tel1 in the absence of Nbs1. Fusion of the Tel1-binding motif of Nbs1 to Mre11 is sufficient to restore Tel1 signaling in nbs1Î cells. Tel1 overexpression does not restore Tel1 signaling in cells carrying the rad50-I1192W mutation, which impairs the ability of Mre11-Rad50 to form the ATP-bound closed conformation. From these findings, we propose that Tel1 has a high-affinity interaction with the C-terminus of Nbs1 and a low-affinity association with Mre11-Rad50, which together accomplish efficient localization and activation of Tel1 at DSBs and telomeres.
KEYWORDS: {{ getKeywords(articleDetailText.words) }}
Sample name | Organism | Experiment title | Sample type | Library instrument | Attributes | |||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
{{attr}} | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
{{ dataList.sampleTitle }} | {{ dataList.organism }} | {{ dataList.expermentTitle }} | {{ dataList.sampleType }} | {{ dataList.libraryInstrument }} | {{ showAttributeName(index,attr,dataList.attributes) }} |
{{ list.authorName }} {{ list.authorName }} |