Grundy, Gabrielle J, Rulten, Stuart L, Arribas-Bosacoma, Raquel, Davidson, Kathryn, Kozik, Zuzanna, Oliver, Antony W, Pearl, Laurence H and Caldecott, Keith W (2016) The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins. Nature Communications, 7. a11242. ISSN 2041-1723
![]() |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (2MB) |
Abstract
The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a related but functionally distinct motif in XLF, WRN, MRI and PAXX, which we denote the XLF-like motif. We show that WRN possesses two KBMs; one at the N terminus next to the exonuclease domain and one at the C terminus next to an XLF-like motif. We reveal that the WRN C-terminal KBM and XLF-like motif function cooperatively to bind Ku complexes and that the N-terminal KBM mediates Ku-dependent stimulation of WRN exonuclease activity. We also show that WRN accelerates DSB repair by a mechanism requiring both KBMs, demonstrating the importance of WRN interaction with Ku. These data define a conserved family of KBMs that function as molecular tethers to recruit and/or stimulate enzymes during NHEJ.
Item Type: | Article |
---|---|
Schools and Departments: | School of Life Sciences > Sussex Centre for Genome Damage and Stability |
Subjects: | Q Science > Q Science (General) |
Depositing User: | Nikoleta Kiapidou |
Date Deposited: | 20 Apr 2016 11:04 |
Last Modified: | 15 Mar 2017 03:57 |
URI: | http://srodev.sussex.ac.uk/id/eprint/60563 |
View download statistics for this item
📧 Request an updateProject Name | Sussex Project Number | Funder | Funder Ref |
---|---|---|---|
Non-homologous End-Joining Protein Complexes and Genome Stability | G1305 | CANCER RESEARCH UK | C6563/A16771 |
Structural Biology of DNA Damage Response and Repair Mechanisms and its Exploitation for Drug Discov | G0891 | CANCER RESEARCH UK | C302/A14532 |