Strand-biased cytosine deamination at the replication fork causes cytosine to thymine mutations in Escherichia coli.

ABSTRACT: The rate of cytosine deamination is much higher in single-stranded DNA (ssDNA) than in double-stranded DNA, and copying the resulting uracils causes C to T mutations. To study this phenomenon, the catalytic domain of APOBEC3G (A3G-CTD), an ssDNA-specific cytosine deaminase, was expressed in an Escherichia coli strain defective in uracil repair (ung mutant), and the mutations that accumulated over thousands of generations were determined by whole-genome sequencing. C:G to T:A transitions dominated, with significantly more cytosines mutated to thymine in the lagging-strand template (LGST) than in the leading-strand template (LDST). This strand bias was present in both repair-defective and repair-proficient cells and was strongest and highly significant in cells expressing A3G-CTD. These resu

SUBMITTER: Bhagwat AS 

PROVIDER: S-EPMC4776466 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature