Zachary F. Pursell

TL;DR: An extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations, uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load.

TL;DR: A new mechanism of cancer progression is suggested in which mutations develop in a rapid burst after ablation of replication repair, which implies a threshold compatible with cancer-cell survival.

TL;DR: Tumors with somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT→TAT and TCG→TTG mutations and overall mutation frequencies often exceeding 100 mutations/Mb.

TL;DR: It is reported here that the concentrations of the four dNTPs are not equal in mitochondria isolated from several tissues of both young and old rats, and this data, plus some published data on specific mitochondrial mutations seen in human diseases, are consistent with the hypothesis that normal intramitochondrial dN TP pool asymmetries may contribute to spontaneous mutagenesis in the mammalian mitochondrial genome.

TL;DR: It is found that, overall, MMR most efficiently corrects the most potentially deleterious errors (indels) and then the most common substitution mismatches.