The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins.
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Date
2016-04-11ICR Author
Author
Grundy, GJ
Rulten, SL
Arribas-Bosacoma, R
Davidson, K
Kozik, Z
Oliver, AW
Pearl, LH
Caldecott, KW
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
DNA Damage
Exodeoxyribonucleases
DNA-Binding Proteins
Antigens, Nuclear
Amino Acid Sequence
Amino Acid Motifs
Conserved Sequence
Protein Structure, Tertiary
Protein Binding
Models, Biological
Molecular Sequence Data
RecQ Helicases
DNA Breaks, Double-Stranded
DNA End-Joining Repair
Ku Autoantigen
Werner Syndrome Helicase
Language
eng
Date accepted
2016-03-04
License start date
2016-04-11
Citation
Nature communications, 2016, 7 pp. 11242 - ?
Publisher
NATURE PUBLISHING GROUP