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Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and Induces DNA strand break resealing.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2004 Feb 13; Vol. 279 (7), pp. 5244-8. Date of Electronic Publication: 2003 Dec 29. - Publication Year :
- 2004
-
Abstract
- Regulating the topological state of DNA is a vital function of the enzyme DNA topoisomerase I. However, when acting on damaged DNA, topoisomerase I may get trapped in a covalent complex with nicked DNA (stalled topoisomerase I), that, if unrepaired, may lead to genomic instability or cell death. Here we show that ADP-ribose polymers target specific domains of topoisomerase I and reprogram the enzyme to remove itself from cleaved DNA and close the resulting gap. Two members of the poly(ADP-ribose) polymerase family, PARP-1 and 2, act as poly(ADP-ribose) carriers to stalled topoisomerase I sites and induce efficient repair of enzyme-associated DNA strand breaks. Thus, by counteracting topoisomerase I-induced DNA damage, PARP-1 and PARP-2 act as positive regulators of genomic stability in eukaryotic cells.
- Subjects :
- Amino Acid Sequence
Base Sequence
Enzyme Activation
Humans
Kinetics
Molecular Sequence Data
Poly(ADP-ribose) Polymerases metabolism
Protein Binding
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Time Factors
DNA Damage
DNA Repair
DNA Topoisomerases, Type I metabolism
Poly Adenosine Diphosphate Ribose metabolism
Poly(ADP-ribose) Polymerases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 279
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 14699148
- Full Text :
- https://doi.org/10.1074/jbc.C300437200