Abstract
DNaseY, a Ca2+- and Mg2+-dependent endonuclease, has been implicated in apoptotic DNA degradation; however, the molecular mechanisms controlling its involvement in this process have not been fully elucidated. We have obtained evidence from yeast two-hybrid screening and coimmunoprecipitation experiments that DNaseY interacted physically with actinin-α4 and this interaction significantly enhanced its endonuclease activity. Accordingly, simultaneous overexpression of both proteins in PC12 cells dramatically increased the rate of apoptosis in response to teniposide' VM26. However, overexpression of DNaseY alone neither triggered apoptosis nor facilitated cell death in response to VM26 or serum deprivation. Instead, the overexpression of DNaseY increased the production of single-strand DNA breaks and evoked a profound upregulation of DNA repair pathways. Taken together, our results point to a novel regulatory mechanism of DNaseY activity and offer an explanation for why cells must first cleave key DNA repair and replication proteins before the successful execution of apoptosis.
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Abbreviations
- MARs:
-
matrix attachment regions
- ssb:
-
single-strand break
- BUR:
-
base-unpairing region
- ds:
-
double strand
- ss:
-
single strand
- XRCC1:
-
X-ray repair cross complementing 1
- Polβ:
-
DNA polymerase β
- Lig3:
-
DNA ligase 3
- Polδ/ɛ:
-
DNA polymerase δ/ɛ
- PCNA:
-
proliferating cell nuclear antigen
- Lig1:
-
DNA ligase1
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We thank Joanne Chartier and Min Wang for their technical assistance.
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Liu, Q., Lei, J., LeBlanc, J. et al. Regulation of DNaseY activity by actinin-α4 during apoptosis. Cell Death Differ 11, 645–654 (2004). https://doi.org/10.1038/sj.cdd.4401401
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DOI: https://doi.org/10.1038/sj.cdd.4401401
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