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 (1). a11242. ISSN 2041-1723

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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:	10 Aug 2020 11:45
URI:	http://sro.sussex.ac.uk/id/eprint/60563

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