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

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García-Rubio, María

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Shaltz, Samantha

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Aguilera, Andrés

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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

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1568-7856

dc.identifier.uri

https://hdl.handle.net/10161/30370

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

DNA repair

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10.1016/j.dnarep.2023.103489

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Saccharomyces cerevisiae

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Cytosine

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Uracil

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DNA

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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

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Basic Science Departments

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Institutes and Centers

pubs.organisational-group

Molecular Genetics and Microbiology

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Duke Cancer Institute

pubs.publication-status

Published

pubs.volume

126

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