| First Author | Kaushik Tiwari M | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 19 | Pages | 8979-94 |
| PubMed ID | 23913414 | Mgi Jnum | J:210762 |
| Mgi Id | MGI:5571803 | Doi | 10.1093/nar/gkt670 |
| Citation | Kaushik Tiwari M, et al. (2013) XPD-dependent activation of apoptosis in response to triplex-induced DNA damage. Nucleic Acids Res 41(19):8979-94 |
| abstractText | DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of gammaH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with gammaH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation. |
