Hypermutability of Damaged Single-Strand DNA in Yeast
Author Information
Author(s): Yang Yong, Sterling Joan, Francesca Resnick, Michael A. Gordenin, Orna Cohen-Fix
Primary Institution: National Institute of Environmental Health Sciences, National Institutes of Health
Hypothesis
Lesions in transient single-strand stretches of chromosomal DNA are expected to be especially threatening to genome stability.
Conclusion
The study found that long stretches of single-strand DNA formed at double-strand breaks and uncapped telomeres are hypermutable and can lead to multiple mutations.
Supporting Evidence
- Lesions induced by UV-light and methyl methanesulfonate can be tolerated in long single-strand regions and are hypermutagenic.
- The hypermutability required PCNA monoubiquitination and was largely attributable to translesion synthesis by the error-prone DNA polymerase ΞΆ.
- Analysis of the UV-induced mutants revealed strong strand-specific bias and unexpectedly high frequency of alleles with widely separated multiple mutations.
Takeaway
When DNA gets damaged, some parts can become really good at making mistakes when they try to fix themselves, which can lead to lots of changes in the DNA.
Methodology
The researchers used yeast to create systems that generate long stretches of single-strand DNA next to double-strand breaks or uncapped telomeres and analyzed the resulting mutations.
Limitations
The study primarily focuses on yeast, which may not fully represent the same processes in other organisms.
Statistical Information
P-Value
p<0.02
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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