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  • The EMBO Journal (2003) 22, 3451 - 3460
  • doi:10.1093/emboj/cdg320

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

  1. Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309 USA
  2. Present address: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA
  3. Division of Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA

Correspondence to:

Ding Xue, E-mail: ding.xue@colorado.edu

Received 14 March 2003; Accepted 12 May 2003; Revised 28 April 2003

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.

  • Keywords:

    • apoptosis,
    • Caenorhabditis elegans,
    • DNA degradation,
    • EndoG,
    • Fen-1