A trio of research papers from Stanford Medicine researchers and their international collaborators transforms scientists' understanding of how small DNA circles -; until recently dismissed as inconsequential -; are major drivers of many types of human cancers.
Stanford Medicine Nov 6 2024 A trio of research papers from Stanford Medicine researchers and their international collaborators transforms scientists' understanding of how small DNA circles -; until recently dismissed as inconsequential -; are major drivers of many types of human cancers.
Mischel is co-senior author of each of the three papers; Howard Chang, MD, PhD, professor of dermatology and genetics, the Virginia and D.K. Ludwig Professor in Cancer Research and a Howard Hughes Medical Institute investigator, is the co-senior author of two of the three papers and a co-author on the third paper.
The researchers also showed that the circles can contain not just cancer-driving oncogenes and genes that modulate the immune response, but also that others can contain only DNA sequences called enhancers that drive the expression of genes on other circles by linking two or more ecDNAs together. Mischel and Chang are the co-senior authors of the second paper that studied how the ecDNA circles are segregated into daughter cells when cancer cells divide. Typically, ecDNAs segregate randomly during cell division. As a result, some new cells could have many ecDNAs while their sister cells had none.
These jackpot events highlight a weakness in the cancer cells, however. Chang and Mischel and the eDyNAmiC team realized that there is inherent tension between transcription and replication, each of which are carried out by protein machinery that trundles along the DNA strand. When transcription and replication machinery collide, the process stalls and the cell activates internal checkpoints to pause cell division until the conflict is resolved.
DNA Medicine Cancer Therapy Cell Cell Division Dermatology Evolution Genes Genetic Genetics Metastasis Oncogene Oncology Pathology Protein Research Transcription Tumor
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