SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage.
Ubiquitin/26S proteasome-dependent degradation of topoisomerase I (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage. In the current study, we show that treatment of mammalian cells or yeast cells expressing human DNA TOP1 with camptothecin (CPT) induces covalent modification of the TOP1 by SUMO-1/Smt3p, a ubiquitin-like protein. This conclusion is based on the following observations: (i) Mammalian DNA TOP1 conjugates induced by CPT were cross-reactive with SUMO-1/Smt3p-specific antibodies both in yeast expressing human DNA TOP1 as well as mammalian cells. (ii) The formation of TOP1 conjugates was shown to be dependent on UBC9, the E2 enzyme for SUMO-1/Smt3p. (iii) TOP1 physically interacts with UBC9. (iv) Ubc9 mutant yeast cells expressing human DNA TOP1 was hypersensitive to CPT, suggesting that UBC9/SUMO-1 may be involved in the repair of TOP1-mediated DNA damage.
Mao
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Y
Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Sun
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M
Desai
S D
SD
Liu
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LF
D004249:DNA Damage; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D025842:SUMO-1 Protein; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D012097:Repressor Proteins; C099362:SMT3 protein, S cerevisiae; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D004264:DNA Topoisomerases, Type I; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9