Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.
dc.contributor.author | Williams, Jonathan D | |
dc.contributor.author | Zhu, Demi | |
dc.contributor.author | García-Rubio, María | |
dc.contributor.author | Shaltz, Samantha | |
dc.contributor.author | Aguilera, Andrés | |
dc.contributor.author | Jinks-Robertson, Sue | |
dc.date.accessioned | 2024-03-19T14:53:30Z | |
dc.date.available | 2024-03-19T14:53:30Z | |
dc.date.issued | 2023-06 | |
dc.description.abstract | Transcription in Saccharomyces cerevisiae is associated with elevated mutation and this partially reflects enhanced damage of the corresponding DNA. Spontaneous deamination of cytosine to uracil leads to CG>TA mutations that provide a strand-specific read-out of damage in strains that lack the ability to remove uracil from DNA. Using the CAN1 forward mutation reporter, we found that C>T and G>A mutations, which reflect deamination of the non-transcribed and transcribed DNA strands, respectively, occurred at similar rates under low-transcription conditions. By contrast, the rate of C>T mutations was 3-fold higher than G>A mutations under high-transcription conditions, demonstrating biased deamination of the non-transcribed strand (NTS). The NTS is transiently single-stranded within the ∼15 bp transcription bubble, or a more extensive region of the NTS can be exposed as part of an R-loop that can form behind RNA polymerase. Neither the deletion of genes whose products restrain R-loop formation nor the over-expression of RNase H1, which degrades R-loops, reduced the biased deamination of the NTS, and no transcription-associated R-loop formation at CAN1 was detected. These results suggest that the NTS within the transcription bubble is a target for spontaneous deamination and likely other types of DNA damage. | |
dc.identifier | S1568-7864(23)00043-5 | |
dc.identifier.issn | 1568-7864 | |
dc.identifier.issn | 1568-7856 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Elsevier BV | |
dc.relation.ispartof | DNA repair | |
dc.relation.isversionof | 10.1016/j.dnarep.2023.103489 | |
dc.rights.uri | ||
dc.subject | Saccharomyces cerevisiae | |
dc.subject | Cytosine | |
dc.subject | Uracil | |
dc.subject | DNA | |
dc.subject | Deamination | |
dc.title | Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast. | |
dc.type | Journal article | |
duke.contributor.orcid | Jinks-Robertson, Sue|0000-0001-5924-5852 | |
pubs.begin-page | 103489 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Staff | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Molecular Genetics and Microbiology | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.publication-status | Published | |
pubs.volume | 126 |
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