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

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posted on 2023-06-08, 22:33 authored by Jessica HudsonJessica Hudson, Shih-Chieh Chiang, Owen Wells, Chris Rookyard, Sherif F El-Khamisy
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.

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Publication status

  • Published

File Version

  • Published version

Journal

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

ISSN

2041-1723

Publisher

Nature Communications

Volume

3

Page range

733

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-09-17

First Open Access (FOA) Date

2015-09-17

First Compliant Deposit (FCD) Date

2015-09-17

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