CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-6/EndoG to promote apoptotic DNA degradation
Jay Z. Parrish1,2,
Chonglin Yang1,
Binghui Shen3, and
Ding Xue1,4
1 Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309 and 3 Division of Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA 2 Present address: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA 4 Corresponding author e-mail: ding.xue{at}colorado.edu
Abstract:
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.
Key Words: Keywords: apoptosis/Caenorhabditis elegans/DNA degradation/EndoG/Fen-1
