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  • Biologist publishes research on DNA replication-transcription conflicts

Biologist publishes research on DNA replication-transcription conflicts

Tuesday, October 12, 2021

Patricia Foster.
Patricia L. Foster. Photo by Indiana University

Patricia L. Foster, professor emerita of Indiana University College of Arts and Sciences' Department of Biology, is the first author on an article in the American Society for Microbiology's journal mBio.

DNA replication and transcription occur on the same DNA template, making it likely for frequent encounters between the two machines. Genomic disruption can occur when the encounters are head-to-head; however, it is debatable whether such replication-transcription conflicts contribute to spontaneous mutations.

Foster and her colleagues analyzed in detail a large collection of mutations generated with mismatch repair-defective strains of Escherichia coli bacteria. They discovered that across the genome there are no significant differences in mutation frequencies between genes oriented codirectionally and those oriented head-on to replication.

Cross section of Escherichia coli bacteria under transmission electron microscopy. Adobe Stock photo #196637990
Cross section of Escherichia coli bacteria under transmission electron microscopy. Adobe Stock photo #196637990

The researchers found a 2- to 3-fold bias for small insertions and deletions in head-on-oriented genes among a subset of highly expressed genes, but this difference was almost entirely due to the asymmetrical locations of tRNA genes containing mononucleotide runs, which are hot spots for these mutations.

Foster and colleagues concluded that biases in the positions of mutational target sequences can account for most, if not all, apparent biases in mutation frequencies between genes oriented head-on and codirectionally to replication.

Coauthors of the study were Heewook Lee (Ph.D. student in the IU Luddy School of Informatics, Computing, and Engineering at the time of the study) and Brittany A. Niccum (microbiology Ph.D. student in Foster's lab at the time of the study).

U.S. Army Research Office Multidisciplinary University Research Initiative (MURI) award (to Foster and Lee) and National Institutes of Health funding (to Niccum) provided support for the research.

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