"The Deubiquitinating Enzyme Doa4p Protects Cells from DNA Topoisomerase I Poisons"

Hervé Jacquiau, Ph.D. is one of the authors on this article on how the DNA topoisomerase I (Top1p) catalyzes changes in DNA topology via the formation of an enzyme-DNA covalent complex that is reversibly stabilized by the antitumor drug, camptothecin (CPT). During S-phase, collisions with replication forks convert these complexes into cytotoxic DNA lesions that trigger cell cycle arrest and cell death. To investigate cellular responses to CPT-induced DNA damage, a yeast genetic screen identified conditional tah mutants with enhanced sensitivity to self-poisoning DNA topoisomerase I mutant (Top1T722Ap), which mimics the action of CPT. Mutant alleles of three genes, DOA4, SLA1 and SLA2, were recovered. Through these findings  a functional link is indicated between ubiquitin-mediated proteolysis and cellular resistance to CPT-induced DNA damage.

Hervé Jacquiau, Ph.D., assists in all aspects of patent practice, including patent prosecution and litigation. His background covers a variety of technologies, particularly biotechnology, bioengineering, biochemistry, molecular biology and microbiology. Hervé received his Ph.D. degree from the University of Cambridge after investigating the genetic and biochemical features responsible for the biodegradation of toxic pollutants.

To read the full article, click the link below: