Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links. 2916 Feb 98

Recently, ZATT (also known as ZNF451 or Zpf451) was reported by Schellenberg et al. to aid the removal of Topoisomerase II cleavage complexes by stimulating the phosphodiesterase activity of Tyrosyl DNA Phosphodiesterase 2. Although the full implication of this discovery is unknown, it will help us understand how cells respond to topoisomerase-induced genome damage and chemotherapeutic topoisomerase 'poisons'.
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PMID:TDP2, TOP2, and SUMO: what is ZATT about? 2891 34