MutS? Stimulates Holliday Junction Resolution by the SMX Complex.

MutS? and MutS? play important roles in DNA mismatch repair and are linked to inheritable cancers and degenerative disorders. Here, we show that MSH2 and MSH3, the two components of MutS?, bind SLX4 protein, a scaffold for the assembly of the SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX) trinuclease complex. SMX promotes the resolution of ...
Holliday junctions (HJs), which are intermediates in homologous recombinational repair. We find that MutS? binds HJs and stimulates their resolution by SLX1-SLX4 or SMX in reactions dependent upon direct interactions between MutS? and SLX4. In contrast, MutS? does not stimulate HJ resolution. MSH3-depleted cells exhibit reduced sister chromatid exchanges and elevated levels of homologous recombination ultrafine bridges (HR-UFBs) at mitosis, consistent with defects in the processing of recombination intermediates. These results demonstrate a role for MutS? in addition to its established role in the pathogenic expansion of CAG/CTG trinucleotide repeats, which is causative of myotonic dystrophy and Huntington's disease.
Mesh Terms:
DNA Repair, DNA Replication, DNA-Binding Proteins, Endodeoxyribonucleases, Endonucleases, Genomic Instability, HEK293 Cells, Holliday Junction Resolvases, Humans, MutS Homolog 2 Protein, MutS Homolog 3 Protein, MutS Proteins, Protein Binding, Recombinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cell Rep
Date: Dec. 20, 2019
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