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Involvement of Exo1b in DNA damage-induced apoptosis

Bolderson, Emma, Richard, Derek J., Edelmann, Winfried, & Khanna, Kum Kum (2009) Involvement of Exo1b in DNA damage-induced apoptosis. Nucleic Acids Research, 37(10), pp. 3452-3463.

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Abstract

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

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15 citations in Scopus
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14 citations in Web of Science®

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ID Code: 40634
Item Type: Journal Article
Keywords: Apoptosis, inherited genomic integrity, DNA damage-induced , cell survival
DOI: 10.1093/nar/gkp194
ISSN: 0305-1048
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2009 Oxford University Press
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 10 Mar 2011 10:44
Last Modified: 01 Mar 2012 00:31

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