Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published June 1, 2023 | public
Journal Article

Deletions of DNA in cancer and their possible uses for therapy


Despite advances in treatments over the last decades, a uniformly reliable and free of side effects therapy of human cancers remains to be achieved. During chromosome replication, a premature halt of two converging DNA replication forks would cause incomplete replication and a cytotoxic chromosome nondisjunction during mitosis. In contrast to normal cells, most cancer cells bear numerous DNA deletions. A homozygous deletion permanently marks a cell and its descendants. Here, we propose an approach to cancer therapy in which a pair of sequence-specific roadblocks is placed solely at two cancer-confined deletion sites that are located ahead of two converging replication forks. We describe this method, termed "replication blocks specific for deletions" (RBSD), and another deletions-based approach as well. RBSD can be expanded by placing pairs of replication roadblocks on several different chromosomes. The resulting simultaneous nondisjunctions of these chromosomes in cancer cells would further increase the cancer-specific toxicity of RBSD.

Additional Information

© 2023 Wiley Periodicals LLC. The authors thank David Chan, Robert Hoffman, Nils Johnsson, Michael Lynch, David Prober, and David Tirrell for helpful comments on the manuscript. AUTHOR CONTRIBUTIONS. Alexander Varshavsky conceived RBSD. Alexander Varshavsky and Kim Lewis conceived UBD. Alexander Varshavsky, Kim Lewis, and Shun-Jia Chen discussed these strategies, with Shun-Jia Chen contributing to designs of replication roadblocks. Alexander Varshavsky, Kim Lewis, and Shun-Jia Chen wrote the paper. DATA AVAILABILITY STATEMENT. Data derived from public domain resources. The authors declare no conflicts of interest.

Additional details

August 22, 2023
December 22, 2023