MutSβ stimulates Holliday junction resolution by the SMX complex
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Sarah Young Marie Sebald Rajvee Shah Punatar Meghan Larin Laura Masino Monica Rodrigo Brenni Eric Chih-Chao Liang Stephen WestAbstract
MutSα and MutSβ 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 MutSβ, 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 MutSβ binds HJs and stimulates their resolution by SLX1-SLX4 or SMX in reactions dependent upon direct interactions between MutSβ and SLX4. In contrast, MutSα 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 MutSβ 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.
Journal details
Journal Cell Reports
Volume 33
Issue number 3
Pages 108289
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.celrep.2020.108289
Figshare View on figshare
Europe PubMed Central 33086055
Pubmed 33086055