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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair
Nature Communications, Volume 3, Article 733, Year 2012
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Description
Breaking and sealing one strand of DNA is an inherent feature of chromosome metabolism to overcome torsional barriers. Failure to reseal broken DNA strands results in protein-linked DNA breaks, causing neurodegeneration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1), which removes stalled topoisomerase 1 peptides from DNA termini. Here we show that TDP1 is a substrate for modification by the small ubiquitin-like modifier SUMO. We purify SUMOylated TDP1 from mammalian cells and identify the SUMOylation site as lysine 111. While SUMOylation exhibits no impact on TDP1 catalytic activity, it promotes its accumulation at sites of DNA damage. A TDP1 SUMOylation-deficient mutant displays a reduced rate of repair of chromosomal single-strand breaks arising from transcription-associated topoisomerase 1 activity or oxidative stress. These data identify a role for SUMO during single-strand break repair, and suggest a mechanism for protecting the nervous system from genotoxic stress. © 2012 Macmillan Publishers Limited. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3316882/bin/ncomms1739-s1.pdf
Authors & Co-Authors
Hudson, Jessica J.R.
United Kingdom, Brighton
Genome Damage and Stability Centre
Chiang, Shihchieh
United Kingdom, Brighton
Genome Damage and Stability Centre
Wells, Owen S.
United Kingdom, Brighton
Genome Damage and Stability Centre
Rookyard, Chris
United Kingdom, Brighton
Genome Damage and Stability Centre
El-Khamisy, Sherif F.
United Kingdom, Brighton
Genome Damage and Stability Centre
Egypt, Cairo
Faculty of Pharmacy - Ain Shams University
Statistics
Citations: 81
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1038/ncomms1739
e-ISSN:
20411723
Research Areas
Genetics And Genomics