Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45.
The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease complex critical for the induction of DNA fragmentation in vitro. To understand the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant mice. DNA fragmentation activity is completely abolished in cell extracts from DFF45 mutant tissues. In response to apoptotic stimuli, splenocytes, thymocytes, and granulocytes from DFF45 mutant mice are resistant to DNA fragmentation, and splenocytes and thymocytes are also resistant to chromatin condensation. Nevertheless, development of the immune system in the DFF45 mutant mice is normal. These results demonstrate that DFF45 is critical for the induction of DNA fragmentation and chromatin condensation in vivo, but is not required for normal immune system development.
Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
J
J
Zhang
X
X
Liu
D C
DC
Scherer
L
L
van Kaer
X
X
Wang
M
M
Xu
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002843:Chromatin / Q000276:immunology; D003001:Cloning, Molecular; D053938:DNA Fragmentation / Q000235:genetics*; D017931:DNA Primers; D003851:Deoxyribonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System / Q000254:growth & development; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D002843:Chromatin; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases