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Karen Vasquez, Ph.D. – VAI Seminar Series

 

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Karen Vasquez, Ph.D. – VAI Seminar Series

October 7 @ 12:00 pm - 1:00 pm

Novel mechanisms of genetic instability in cancer

Repetitive sequences have the capacity to adopt alternative DNA structures (e.g. H-DNA and Z-DNA) and stimulate genetic instability in the absence of exogenous DNA damage. However, the biological significance and the mechanisms of this DNA-structure-induced genetic instability are unknown. Here, we report that H-DNA- and Z-DNA-forming sequences are enriched at translocation breakpoints in human cancer genomes, implicating them in cancer etiology. We found that H-DNA-induced mutations were suppressed in human cells deficient in nucleotide excision repair (NER) nucleases, ERCC1-XPF and XPG, but in contrast, were stimulated in cells deficient in FEN1, a replication-related endonuclease. Further, we found that these nucleases cleaved H-DNA conformations, and simulated their interactions on a modeled H-DNA structure at the sub-molecular level. Interestingly, Z-DNA was not processed in the same fashion as H-DNA, but instead we identified a unique pathway for its mutagenic repair that included the mismatch repair protein complex, MSH2-MSH3 and the NER complex, ERCC1-XPF. These results suggest novel mechanisms of genetic instability triggered by H-DNA and Z-DNA through distinct structure-specific, cleavage-based replication-independent and replication-dependent pathways, and provide critical information on the role that DNA structure itself may play in the etiology of cancer and other human diseases.

For more information about Dr. Vasquez, please visit https://sites.utexas.edu/vasquez/

Speaker Information

Karen Vasquez, Ph.D.
James T. Doluisio Regents Professor
Head, Division of Pharmacology and Toxicology
The University of Texas at Austin
Dell Pediatric Research Institute

Time & Location

12:00 pm on Zoom

Registration is free but required. Please sign up here. After registering, you will receive an email with the Zoom link and passcode.

VAI Host: Piroska Szabó, Ph.D.

Questions?

For questions, please contact Kim Cousineau at 616.234.5684.

Details

Date:
October 7
Time:
12:00 pm - 1:00 pm
Event Category:

Venue

Virtual
MI United States