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Internucleosomal DNA fragmentation in apoptosis may be a cooperative activity between DNA fragmentation factor and the Ca2+‐Mg2+‐dependent endonuclease DNAS1L3
Author(s) -
errami youssef,
Zerfaoui Mourad,
Zhang Jianhua,
Xu Ming,
Boulares Hamid
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb364
Subject(s) - apoptotic dna fragmentation , dna fragmentation , apoptosis , microbiology and biotechnology , endonuclease , biology , fragmentation (computing) , chromatin , programmed cell death , dna , genetics , ecology
Apoptosis or programmed cell death is a key process involved in animal development and tissue homeostasis. Internucleosomal DNA fragmentation (INDF) is a hallmark of apoptosis, in which genomic DNA is first degraded into large 50 kb fragments and then into repeats of 200 bp. Mechanism by which INDF occurs is still unclear. Our studies revealed that this process could involve two endonucleases working cooperatively. The DNA fragmentation factor (DFF), is induced on cleavage of DFF45 (the inhibitory and chaperone subunit of DFF40) by caspase‐3. Several cell lines undergo key apoptotic events including cleavage of DFF45 and of chromatin into large 50 kb fragments but failed to display clear INDF. Such failure did not correlate with the expression levels of DFF40 or 45. Apoptotic cells derived from DFF45− /− mice exhibited neither 50 kb nor INDF. Suggesting that caspase‐3 activation, cleavage of DFF45, and the consequent activation of DFF40 are necessary but not sufficient for INDF. We identified DNAS1L3, a Ca 2+ ‐Mg 2+ ‐dependent endonuclease, as an important apoptotic INDF‐mediating enzyme. Here, we show, that DNAS1L3 translocates from the endoplasmic reticulum (ER) to the nucleus upon etoposide exposure. And interestingly, DFF40 and DFF45 were required for DNAS1L3‐mediated INDF. Altogether, our results show that DNAS1L3 translocates to the nucleus upon apoptotic stimulus and cooperates with DFF40 to mediate INDF.