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.

Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and induces DNA strand break resealing / Malanga, Maria; F. R., Althaus. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 279:(2004), pp. 5244-5248.

Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and induces DNA strand break resealing

MALANGA, MARIA;
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.
2004
Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and induces DNA strand break resealing / Malanga, Maria; F. R., Althaus. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 279:(2004), pp. 5244-5248.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/204668
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