title: CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-6/EndoG to promote apoptotic DNA degradation.
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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Parrish
authors.forename: Chonglin
authors.initials: C
authors.lastname: Yang
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
authors.forename: Ding
authors.initials: D
authors.lastname: Xue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006868:Hydrolysis; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; C469544:Cps-6 protein, C elegans; D017931:DNA Primers; D024101:Mitochondrial Proteins; D004247:DNA; C476219:CRN-1 protein, C elegans; D004706:Endodeoxyribonucleases