Abstract
The speaker’s laboratory has discovered a large family of small extrachromosomal circles of DNA present in normal and cancer cells, microDNA that are ubiquitous, 100-400 bp long and derived from transcriptionally active parts of the genome. In this lecture, the speaker will give an update of his research, including applications for liquid biopsy. The origin recognition complex (ORC), is a complex of six subunit proteins (ORC1-ORC6) that has been considered essential for DNA replication in eukaryotes. He will report his surprising discovery that several human cancer cell lines survive and replicate normally despite the complete absence of ORC1 and ORC2 subunits. This result suggests that at least in human cancer cells, there may be a mechanism to bypass the strict requirement for ORC to initiate DNA replication. Finally, ASF1a has been studied for some time as a histone chaperone. He will report that ASF1a has a role independent of its histone chaperone activity in promoting nonhomologous end joining (NHEJ) mediated repair of double strand DNA breaks (DSB). Since 10% of prostate cancers or diffuse large B cell lymphomas suffer from a homozygous deletion of ASF1a gene, this result suggests the speaker and his research group to use ASF1a as a biomarker to identify patients whose tumors will be particularly responsive to DSB inducing chemotherapy or radiotherapy.
About the speaker
Prof Anindya Dutta received his PhD in Viral Oncology from the Rockefeller University in 1989 and joined the Medical School in Harvard University as an Assistant Professor in 1993. In 2003, he moved to the University of Virginia and is currently the Harry F Byrd Professor and Chair of Biochemistry and Molecular Genetics.
Prof Dutta’s research includes discovering the key regulatory proteins that initiate replication of chromosomes, as well as factors that prevent cells from over-replicating their DNA. His discoveries have led to a new compound under development that can kill cancer cells by forcing them to over-replicate their DNA. Additional work from his laboratory has shown how microRNAs push our cells to differentiate or to turn into cancers, and how a human papilloma virus oncogene can subvert a cell’s response to DNA damage.
Prof Dutta was elected a member of the American Society for Biochemistry and Molecular Biology, the American Society of Investigative Pathology, the American Society of Cell Biology, the American Association for the Advancement of Science, and the American Association for Cancer Research. He was also elected a Fellow of the American Association of Advancement of Science, and has served on the editorials boards of The Journal of Biological Chemistry, Cancer Biology and Therapy, The Journal of Biochemistry and Cancer Research.
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