CRN‐1, a Caenorhabditis elegans FEN‐1 homologue, cooperates with CPS‐6/EndoG to promote apoptotic DNA degradation

CRN‐1, a Caenorhabditis elegans FEN‐1 homologue, cooperates with CPS‐6/EndoG to promote... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

CRN‐1, a Caenorhabditis elegans FEN‐1 homologue, cooperates with CPS‐6/EndoG to promote apoptotic DNA degradation

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
D.O.I.
10.1093/emboj/cdg320
Publisher site
See Article on Publisher Site

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.

Journal

The EMBO JournalWiley

Published: Jul 1, 2003

References

  • The genetics of Caenorhabditis elegans
    Brenner, Brenner
  • The FEN‐1 family of structure‐specific nucleases in eukaryotic DNA replication, recombination and repair
    Lieber, Lieber

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