Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity

• Published in: eLife Vol. 9
• Main Authors: Sciascia, Nicholas, Wu, Wei, Zong, Dali, Sun, Yilun, Wong, Nancy, John, Sam, Wangsa, Darawalee, Ried, Thomas, Bunting, Samuel F, Pommier, Yves, Nussenzweig, André
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 14.02.2020; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animal experimentation; Animals; Cancer; Cancer cells; Cell cycle; Cell viability; Chemotherapy; Combination drug therapy; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA Damage; DNA Repair; DNA topoisomerase (ATP-hydrolysing); DNA Topoisomerases, Type II - metabolism; Double-strand break repair; Drugs; Enzymes; Etoposide; Genetic research; Genetics and Genomics; Genome - genetics; genome instability; Genomes; Genomic instability; Genomics; Health aspects; Humans; Identity; Lymphocytes B; Mice, Inbred C57BL; Proteasome Endopeptidase Complex - metabolism; Proteasome inhibitors; Proteins; Proteolysis; Spleen; Stress management; topoisomerases; California; mouse; genetics; genome instability; DNA damage; genomics; cancer; topoisomerases; DNA repair; human

Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the c...