Strand-biased cytosine deamination at the replication fork causes cytosine to thymine mutations in Escherichia coli
Abstract
C:G to T:A mutations constitute the largest class of spontaneous base substitutions in all organisms. These mutations are thought to be a result of cytosine deaminations, but what promotes these deaminations is unclear. We confirm here the hypothesis that they occur predominantly in single-stranded DNA (ssDNA) and identify the ssDNA in the lagging strand template as the preferred site of C:G to T:A mutations. As a consequence, replication creates a strand bias in these mutations, and this overwhelms any strand bias resulting from transcription. These results explain a long-recognized bias in base composition of microbial genomes called GC skew and predicts that C:G to T:A mutations created by the APOBEC3 family deaminases in cancer genomes should occur with the same strand bias.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 02, 2016
- Source ID
- 10.1073/pnas.1522325113
Entities
People
- Ashok S. Bhagwat
- Haixu Tang
- Heewook Lee
- Jesse P. Townes
- Patricia L. Foster
- Weilong Hao
Organizations
- Indiana University
- National Institutes of Health
- United States Army
- Wayne State University