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• W2912114930 abstract "5-aza-dC (5-aza-29-deoxycytidine, clinically known as decitabine) is used to treat some hematopoietic malignancies, but its mechanism of action is not defined. Here we identify a role for covalent PARP1-DNA adducts in cell killing by 5-aza-dC. We demonstrate that covalent PARP1- DNA adducts can be recovered from cells treated with 5-aza-dC alone or in combination with a PARP catalytic inhibitor. PARP1-DNA adducts are predominately 89 kD in length, contain the cleaved PARP1 fragment that is a signature of apoptotic cells, and bear the terminal neo-epitope generated by caspase cleavage. Smaller PARP1-DNA adducts bearing the apoptotic neo-epitope were also detected, but not adducts containing full-length PARP1. DNA-adducted PARP1 fragments thus provide a biochemical link between drug-induced PARP1-DNA adduct formation and cell killing. They support a model in which 5-aza-dC causes DNA damage that recruits full- length PARP1, which forms covalent adducts that induce apoptosis, resulting in PARP1 cleavage and cell killing." @default.
• W2912114930 created "2019-02-21" @default.
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• W2912114930 date "2019-02-02" @default.
• W2912114930 modified "2023-09-26" @default.
• W2912114930 title "Treatment with 5-aza-dC Induces Apoptotic PARP1-DNA Adducts" @default.
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