Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.

DNA Repair
Yilun SunYves Pommier

Abstract

Topoisomerases play a pivotal role in ensuring DNA metabolisms during replication, transcription and chromosomal segregation. To manage DNA topology, topoisomerases generate break(s) in the DNA backbone by forming transient enzyme-DNA cleavage complexes (TOPcc) with phosphotyrosyl linkages between DNA ends and topoisomerase catalytic tyrosyl residues. Topoisomerases have been identified as the cellular targets of a variety of anti-cancer drugs (e.g. topotecan, irinotecan, etoposide and doxorubicin, and antibiotics (e.g. ciprofloxacin and levofloxacin). These drugs, as well as other exogenous and endogenous agents, convert the transient TOPcc into persistent TOPcc, which we refer to as topoisomerase DNA-protein crosslinks (TOP-DPC) that challenge genome integrity and lead to cell death if left unrepaired. Proteolysis of the bulky protein component of TOP-DPC (debulking) is a poorly understood repair process employed across eukaryotes. TOP-DPC proteolysis can be achieved either by the ubiquitin-proteasome pathway (UPP) or by non-proteasomal proteases, which are typified by the metalloprotease SPRTN/WSS1. Debulking of TOP-DPC exposes the phosphotyrosyl bonds, hence enables tyrosyl-DNA phosphodiesterases (TDP1 and TDP2) to access a...Continue Reading

References

Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D K Trask, M T Muller
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A Y ChenL F Liu
Mar 22, 1996·The Journal of Biological Chemistry·A LanzaA M Pedrini
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·S W YangH A Nash
Jan 10, 1997·The Journal of Biological Chemistry·P S Kingma, N Osheroff
Sep 26, 1997·The Journal of Biological Chemistry·S D DesaiP D'Arpa
Jul 11, 1998·Molecular Cell·J Sekiguchi, S Shuman
Sep 28, 1998·Biochimica Et Biophysica Acta·G Capranico, M Binaschi
Oct 9, 1998·The Journal of Biological Chemistry·P PourquierY Pommier
Jul 31, 1999·The Journal of Biological Chemistry·Y WangA H Andersen
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·P PourquierY Pommier
Apr 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y MaoL F Liu
Apr 27, 2000·Bioorganic & Medicinal Chemistry Letters·S JinE J LaVoie
Jun 22, 2000·The Journal of Biological Chemistry·Y MaoL F Liu
Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y PommierD M Jerina
Sep 8, 2001·The Journal of Biological Chemistry·Y MaoL F Liu
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·H InterthalJ J Champoux
Nov 9, 2001·The Journal of Biological Chemistry·William A ClibyScott H Kaufmann
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Sep 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Diem-Thu Thieu LesherMatthew R Redinbo
Nov 7, 2002·Current Genetics·Lori LommelKevin S Sweder
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hai XiaoLeroy F Liu

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Citations

May 20, 2021·Biochemistry·Kendra R VannNeil Osheroff
Sep 23, 2021·Nucleic Acids Research·Liton Kumar SahaYves Pommier

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