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PMID: 10759568 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 8 ·2000-04-11 ·Pages 4046-51

Mao Y, Sun M, Desai SD, Liu LF

Abstract

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.

MeSH Terms
DNA Damage DNA Repair DNA Topoisomerases, Type I/metabolism HeLa Cells Humans Ligases/metabolism Protein Binding Repressor Proteins/metabolism SUMO-1 Protein Saccharomyces cerevisiae/enzymology,genetics,metabolism Saccharomyces cerevisiae Proteins Small Ubiquitin-Related Modifier Proteins Ubiquitin-Conjugating Enzymes Ubiquitins/metabolism
Chemicals
Repressor Proteins SMT3 protein, S cerevisiae SUMO-1 Protein SUMO2 protein, human Saccharomyces cerevisiae Proteins Small Ubiquitin-Related Modifier Proteins Ubiquitins Ubiquitin-Conjugating Enzymes DNA Topoisomerases, Type I Ligases ubiquitin-conjugating enzyme UBC9
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mao 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 M
Desai S D
Liu L F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.080536597
Published
2000-04-11
Pages
4046-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18143
Subset
IM
Grants
NCI NIH HHS · R01 CA039662 · United States
NCI NIH HHS · CA39662 · United States
NIGMS NIH HHS · GM27731 · United States
External Links
PubMed source DOI: 10.1073/pnas.080536597 PMC Full Text View journal details
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