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Poly (ADP ribose) polymerase 1 (PARP1) is a critical enzyme involved in DNA damage repair and the regulation of transcription, replication, and cell fate, becoming activated by DNA strand breaks to catalyze poly(ADP ribosyl)ation of itself and other DNA damage response proteins. During apoptosis, PARP1 is cleaved by caspase 3 into an 89 kDa N terminal fragment containing the DNA-binding zinc finger domains and a 24 to 25 kDa C terminal fragment known as cleaved PARP1 (p25), which primarily contains the catalytic domain; this cleavage separates the functional domains, inactivates PARP1s DNA repair capability, and represents a hallmark of programmed cell death. Biologically, PARP1 cleavage functions as a molecular switch from a pro-survival to a pro death state by preventing futile repair of severely damaged DNA, and clinically, increased levels of cleaved PARP1 (p25) are widely used as a marker of apoptosis in research and diagnostic settings, particularly in response to stimuli such as chemotherapy, radiotherapy, and other apoptotic signals.
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