5TVQ

Mouse Tdp2 catalytic domain bound to SUMO2

Summary for 5TVQ

• Entry DOI: 10.2210/pdb5tvq/pdb
• Related: 1WM2 4GZ1 5TVP
• Descriptor: Tyrosyl-DNA phosphodiesterase 2, Small ubiquitin-related modifier 2, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase/dna, dna repair, endonuclease/exonuclease/phosphatase (eep) domain, hydrolase-dna complex, hydrolase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 38841.33

Authors

Schellenberg, M.J.,Williams, R.S. (deposition date: 2016-11-09, release date: 2017-09-27, Last modification date: 2023-10-04)

Primary citation

Schellenberg, M.J.,Lieberman, J.A.,Herrero-Ruiz, A.,Butler, L.R.,Williams, J.G.,Munoz-Cabello, A.M.,Mueller, G.A.,London, R.E.,Cortes-Ledesma, F.,Williams, R.S.
ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
Science, 357:1412-1416, 2017

PubMed Abstract: Topoisomerase 2 (TOP2) DNA transactions proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO (small ubiquitin-related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc. The ZATT SUMO ligase activity further promotes TDP2 interactions with SUMOylated TOP2, regulating efficient TDP2 recruitment through a "split-SIM" SUMO2 engagement platform. These findings uncover a ZATT-TDP2-catalyzed and SUMO2-modulated pathway for direct resolution of TOP2cc.

PubMed: 28912134
DOI: 10.1126/science.aam6468

Experimental method

X-RAY DIFFRACTION (2.35 Å)