Post-translational regulation of Tyrosyl-DNA phosphodiesterase (TDP1 and TDP2) for the repair of the trapped topoisomerase-DNA covalent complex

Interplay between symmetric arginine dimethylation and ubiquitylation regulates TDP1 proteostasis for the repair of topoisomerase I-DNA adducts

“…Post-translational modifications (PTM) ensure efficient propagation of damage signals for DNA repair and genomic integrity (Bhattacharjee et al, 2022;Katyal et al, 2007;Pommier et al, 2016;Shiloh and Ziv, 2013). Several PTMs are important elements in the regulation of TDP1 recruitment, subcellular distribution, and stability of DNA damage response (El-Khamisy, 2011;Chowdhuri and Das, 2021;Pommier et al, 2014).…”

Novel Pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline Derivative Selectively Poisons Leishmania donovani Bisubunit Topoisomerase 1 to Inhibit the Antimony-Resistant Leishmania Infection in Vivo

“…The viability of the Leishmania donovani promastigotes was measured by MTT assay. ,,, All EC 50 values were calculated by using the nonlinear variable slope model for finding EC 50 in Prism (ver. 5.0; GraphPad Software, USA).…”

Synthesis and Biological Activities of 11‐ and 12‐Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB and Tyrosyl‐DNA Phosphodiesterase 1 Inhibitors

“…It can specifically hydrolyze the 3′‐phosphotyrosyl bonds of TOP1ccs to generate DNA breaks with 5′‐hydroxyl and 3′‐phosphate ends for further DNA repair [16,17] . Following the recruitment and activation of poly(ADP‐ribose) polymerase (PARP1), the resulting DNA breaks can be repaired by polynucleotide kinase phosphatase (PNKP), DNA polymerase β and DNA ligase III through the (X‐ray repair complementation group 1) XRCC‐1‐dependent pathway [18–23] . In this pathway, TDP1‐catalyzed hydrolysis of the 3′‐phosphotyrosyl bond is a key step for initiating the repair of TOP1‐mediated DNA damage, which can lead to cancer cell resistance to TOP1 inhibitors [24] .…”

“…[16,17] Following the recruitment and activation of poly(ADP-ribose) polymerase (PARP1), the resulting DNA breaks can be repaired by polynucleotide kinase phosphatase (PNKP), DNA polymerase β and DNA ligase III through the (X-ray repair complementation group 1) XRCC-1-dependent pathway. [18][19][20][21][22][23] In this pathway, TDP1-catalyzed hydrolysis of the 3'-phosphotyrosyl bond is a key step for initiating the repair of TOP1-mediated DNA damage, which can lead to cancer cell resistance to TOP1 inhibitors. [24] Indeed, TDP1-overexpressing cells show resistance to camptothecin (CPT).…”