Scott Gradia

TL;DR: Analysis of the mismatched nucleotide-binding specificity of the hMSH2-hMSH3 and hMSh2-HMSH6 protein complexes showed that they have overlapping but not identical binding specificity, which helps to explain the distribution of mutations in different mismatch-repair genes seen in hereditary nonpolyposis colon cancer.

TL;DR: The results support a model for bidirectional mismatch repair in which stochastic loading of multiple ATP-bound hMSH2-hMSH6 sliding clamps onto mismatch-containing DNA leads to activation of the repair machinery and/or other signaling effectors similar to G protein switches.

TL;DR: This work demonstrates that the pattern of DNA repair following Cas9 cutting at each site is nonrandom and consistent across experimental replicates, cell lines, and reagent delivery methods, and elucidates a strategy for using "error-prone" DNA-repair machinery to generate precise edits.

TL;DR: It is shown that adenine nucleotide binding and hydrolysis by the human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch, suggesting a new model for the function of MutS proteins during mismatch repair in which the switch determines the timing of downstream events.

TL;DR: This work developed a biochemical method (SITE-Seq), using Cas9 programmed with single-guide RNAs (sgRNAs), to identify the sequence of cut sites within genomic DNA, and found that the number of sites identified depended on sgRNA sequence and nuclease concentration.