PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair
View / Open Files
Authors
Ochi, Takashi
Blackford, Andrew
Coates, Julia
Jhujh, Satpal
Mehmood, Shahid
Tamura, Naoka
Travers, Jon
Wu, Qian
Draviam Sastry, Viji
Robinson, Carol V
Publication Date
2015-01-09Journal Title
Science
ISSN
0036-8075
Publisher
American Association for the Advancement of Science
Volume
347
Number
6218
Pages
185-188
Language
English
Type
Article
Metadata
Show full item recordCitation
Ochi, T., Blackford, A., Coates, J., Jhujh, S., Mehmood, S., Tamura, N., Travers, J., et al. (2015). PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science, 347 (6218), 185-188. https://doi.org/10.1126/science.1261971
Abstract
XRCC4 and XLF are two structurally-related proteins that function in DNA double-strand break
(DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF; also called
C9orf142) as a new XRCC4-superfamily member, and show that its crystal structure resembles
that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to
DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX-/-
cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and
cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Kudependent
DNA ligation in vitro, and assembly of core non-homologous end-joining (NHEJ)
factors on damaged chromatin in cells. These findings identify PAXX as a new component of the
NHEJ machinery.
Sponsorship
T.O. and T.L.B. are supported by the Wellcome Trust. The Jackson lab is funded by Cancer
Research UK (CRUK) program grant C6/A11224, the European Research Council and the
European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-
259893 (DDResponse). Core infrastructure funding to the Jackson lab is provided by CRUK
(C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the
University of Cambridge, supplemented by CRUK. V.M.D. is a CRUK Career Development Fellow. The Draviam lab is funded by a CRUK CDA (C28598/A9787).
Funder references
Cancer Research UK (11224)
European Research Council (268536)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (093167/Z/10/Z)
Cancer Research UK (A14492)
Cancer Research UK (A9787)
Identifiers
External DOI: https://doi.org/10.1126/science.1261971
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246822
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved