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Clin Oncol (R Coll Radiol). 2004 Feb;16(1):29-39.

Poly(ADP-ribose) polymerase-1 and ionizing radiation: sensor, signaller and therapeutic target.

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Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, UK.


Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that binds rapidly to single and double-strand breaks in DNA and consequently modifies a range of nuclear proteins involved in the cellular response to ionising radiation. PARP-1 knockout mice are highly sensitive to ionising radiation, and inhibition or depletion of PARP-1 brings about modest sensitisation of cells in culture to radiation doses of 2 Gy and above. In certain cell lines, chemical inhibition of PARP activity is also associated with marked sensitisation to very low doses of radiation (<0.5 Gy). The mechanisms underlying these effects are discussed, and possible therapeutic applications of PARP-1 manipulation in combination with ionising radiation are considered.

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