Structural basis for DNA 3′-end processing by human tyrosyl-DNA phosphodiesterase 1

Fiona J. Flett, Emilija Ruksenaite, Lee A. Armstrong, Shipra Bharati, Roberta Carloni, Elizabeth R. Morris, C. Logan Mackay, Heidrun Interthal () and Julia M. Richardson ()
Additional contact information
Fiona J. Flett: University of Edinburgh
Emilija Ruksenaite: University of Edinburgh
Lee A. Armstrong: University of Edinburgh
Shipra Bharati: University of Edinburgh
Roberta Carloni: University of Edinburgh
Elizabeth R. Morris: University of Edinburgh
C. Logan Mackay: University of Edinburgh
Heidrun Interthal: University of Edinburgh
Julia M. Richardson: University of Edinburgh

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Tyrosyl-DNA phosphodiesterase (Tdp1) is a DNA 3′-end processing enzyme that repairs topoisomerase 1B-induced DNA damage. We use a new tool combining site-specific DNA–protein cross-linking with mass spectrometry to identify Tdp1 interactions with DNA. A conserved phenylalanine (F259) of Tdp1, required for efficient DNA processing in biochemical assays, cross-links to defined positions in DNA substrates. Crystal structures of Tdp1–DNA complexes capture the DNA repair machinery after 3′-end cleavage; these reveal how Tdp1 coordinates the 3′-phosphorylated product of nucleosidase activity and accommodates duplex DNA. A hydrophobic wedge splits the DNA ends, directing the scissile strand through a channel towards the active site. The F259 side-chain stacks against the −3 base pair, delimiting the junction of duplexed and melted DNA, and fixes the scissile strand in the channel. Our results explain why Tdp1 cleavage is non-processive and provide a molecular basis for DNA 3′-end processing by Tdp1.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02530-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02530-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02530-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().