| First Author | Bolderson E | Year | 2009 |
| Journal | Nucleic Acids Res | Volume | 37 |
| Issue | 10 | Pages | 3452-63 |
| PubMed ID | 19339515 | Mgi Jnum | J:173743 |
| Mgi Id | MGI:5050072 | Doi | 10.1093/nar/gkp194 |
| Citation | Bolderson E, et al. (2009) Involvement of Exo1b in DNA damage-induced apoptosis. Nucleic Acids Res 37(10):3452-63 |
| abstractText | 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. |
