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Oligonucleosomal fragmentation of chromosomes in dying cells is a hallmark of apoptosis. Little is known about how it is executed or what cellular components are involved. We show that crn‐1, a Caenorhabditis elegans homologue of human flap endonuclease‐1 (FEN‐1) that is normally involved in DNA replication and repair, is also important for apoptosis. Reduction of crn‐1 activity by RNA interference resulted in cell death phenotypes similar to those displayed by a mutant lacking the mitochondrial endonuclease CPS‐6/endonuclease G. CRN‐1 localizes to nuclei and can associate and cooperate with CPS‐6 to promote stepwise DNA fragmentation, utilizing the endonuclease activity of CPS‐6 and both the 5′–3′ exonuclease activity and a previously uncharacterized gap‐dependent endonuclease activity of CRN‐1. Our results suggest that CRN‐1/FEN‐1 may play a critical role in switching the state of cells from DNA replication/repair to DNA degradation during apoptosis.
The EMBO Journal – Wiley
Published: Jan 1, 2003
Keywords: ; ; ; ;
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