Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.

Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.
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DOI:
10.1016/j.dnarep.2023.103489
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发表时间:
2023-06
期刊:
影响因子:
3.8
通讯作者:
Jinks-Robertson, Sue
Jinks-Robertson, Sue
中科院分区:
医学3区
文献类型:
--
作者:
Williams, Jonathan D.;Zhu, Demi;Shaltz, Samantha;Garcia-Rubio, Maria;Aguilera, Andres;Jinks-Robertson, Sue

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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.
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