Cyril Gary
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Cyril Gary has a total of 7 co-authors. Here are the top co-authors by number of shared publications:
- Andrew Sewell
Department of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA
1 shared publication - Karen S. Anderson
Department of Pharmacology
1 shared publication - Michael Hajek
Department of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA
1 shared publication - Natalia Issaeva
Department of Otolaryngology/Head and Neck Surgery, UNC School of Medicine, Chapel Hill, NC 27599, USA
1 shared publication - Paul G. Cantalupo
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
1 shared publication - Paul G. Cantalupo
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, USA
1 shared publication
Latest Publications
- Open Access
Global Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV-Associated Head and Neck Cancer Cells
High levels of DNA methylation at CpG loci are associated with transcriptional repression of tumor suppressor genes and dysregulation of DNA repair genes. Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC) have high levels of DNA methylation and methylation has been associated with dampening of an innate immune response in virally infected cells. We have been exploring demethylation as a potential treatment in HPV+ HNSCC and recently reported results of a window clinical trial showing that HNSCCs are particularly sensitive to demethylating agent 5-azacytidine (5-aza). Mechanistically, sensitivity is partially due to downregulation of HPV genes expression and restoration of tumor suppressors p53 and Rb. Here, for the first time, we show that 5-azaC treatment of HPV+ HNSCC induces replication and transcription-associated DNA double strand breaks (DSBs) that occur preferentially at demethylated genomic DNA. Blocking replication or transcription prevented formation of DNA DSBs and reduced sensitivity of HPV-positive head and neck cancer cells to 5-azaC, demonstrating that both replication and active transcription are required for formation of DSBs associated with 5-azaC.
Open AccessGlobal Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV-Associated Head and Neck Cancer Cells
High levels of DNA methylation at CpG loci are associated with transcriptional repression of tumor suppressor genes and dysregulation of DNA repair genes. Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC) have high levels of DNA methylation and methylation has been associated with dampening of an innate immune response in virally infected cells. We have been exploring demethylation as a potential treatment in HPV+ HNSCC and recently reported results of a window clinical trial showing that HNSCCs are particularly sensitive to demethylating agent 5-azacytidine (5-aza). Mechanistically, sensitivity is partially due to downregulation of HPV genes expression and restoration of tumor suppressors p53 and Rb. Here, for the first time, we show that 5-azaC treatment of HPV+ HNSCC induces replication and transcription-associated DNA double strand breaks (DSBs) that occur preferentially at demethylated genomic DNA. Blocking replication or transcription prevented formation of DNA DSBs and reduced sensitivity of HPV-positive head and neck cancer cells to 5-azaC, demonstrating that both replication and active transcription are required for formation of DSBs associated with 5-azaC.