The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins.
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ICR Authors
Authors
Grundy, GJ
Rulten, SL
Arribas-Bosacoma, R
Davidson, K
Kozik, Z
Oliver, AW
Pearl, LH
Caldecott, KW
Rulten, SL
Arribas-Bosacoma, R
Davidson, K
Kozik, Z
Oliver, AW
Pearl, LH
Caldecott, KW
Document Type
Journal Article
Date
2016-04-11
Date Accepted
2016-03-04
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.
Citation
Nature communications, 2016, 7 pp. 11242 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
eISSN
2041-1723