SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair

Hudson, Jessica J R, Chiang, Shih-Chieh, Wells, Owen S, Rookyard, Chris and El-Khamisy, Sherif F (2012) SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair., 3. p. 733. ISSN 2041-1723

[img]
Preview
PDF (SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair.) - Published Version
Download (2MB) | Preview

Abstract

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.

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: Owen Wells
Date Deposited: 17 Sep 2015 14:04
Last Modified: 06 Mar 2017 15:30
URI: http://sro.sussex.ac.uk/id/eprint/56807

View download statistics for this item

📧 Request an update