Mutational signatures of redox stress in yeast single-strand DNA and of aging in human mitochondrial DNA share a common feature

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000263

Natalya P. Degtyareva, Natalie Saini, Joan F. Sterling, Victoria C. Placentra, Leszek J. Klimczak, Dmitry A. Gordenin, Paul W. Doetsch

• The authors report on the mutational spectra of redox stress in single-stranded DNA of budding yeast and in human mitochondrial DNA in the context of healthy aging, finding that the predominance of C>T transitions is a predominant feature in both.
• The authors find that the frequencies of hydrogen peroxide-induced mutations in proof-reading deficient yeast mutants supports the conclusion that this form of mutagenesis is the result of direct damage to DNA, rather than misincorporation errors.
• They propose that mutations may occur to the heavy strand of mtDNA when DNA replication starts at the light chain, temporarily making the displaced, heavy strand more vulnerable to damage.