title: Triplex-induced DNA damage response.
abstract: Cellular DNA damage response is critical to preserving genomic integrity following exposure to genotoxic stress. A complex series of networks and signaling pathways become activated after DNA damage and trigger the appropriate cellular response, including cell cycle arrest, DNA repair, and apoptosis. The response elicited is dependent upon the type and extent of damage sustained, with the ultimate goal of preventing propagation of the damaged DNA. A major focus of our studies is to determine the cellular pathways involved in processing damage induced by altered helical structures, specifically triplexes. Our lab has demonstrated that the TFIIH factor XPD occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. We have shown that XPD co-localizes with γH2AX, and its presence is required for the phosphorylation of H2AX tyrosine142, which stimulates the signaling pathway to recruit pro-apoptotic factors to the damage site. Herein, we examine the cellular pathways activated in response to triplex formation and discuss our finding that suggests that XPD-dependent apoptosis plays a role in preserving genomic integrity in the presence of excessive structurally induced DNA damage.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Faye A
authors.initials: FA
authors.lastname: Rogers
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Meetu Kaushik
authors.initials: MK
authors.lastname: Tiwari
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; C051802:triplex DNA; D004247:DNA; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: DNA repair; H-DNA; H2AX; XPD; apoptosis; genomic instability; nucleotide excision repair; triplex DNA; triplex-forming oligonucleotides