Dynamic control of strand excision during human DNA mismatch repair
SCIE
SCOPUS
- Title
- Dynamic control of strand excision during human DNA mismatch repair
- Authors
- Jeon, Y; Kim, D; Martin-Lopez, JV; Lee, R; Oh, J; Hanne, J; Fishel, R; Lee, JB
- Date Issued
- 2016-03-22
- Publisher
- National academy of sciences
- Abstract
- Mismatch repair (MMR) is activated by evolutionarily conserved MutS homologs (MSH) and MutL homologs (MLH/PMS). MSH recognizes mismatched nucleotides and form extremely stable sliding clamps that may be bound by MLH/PMS to ultimately authorize strand-specific excision starting at a distant 3'- or 5'-DNA scission. The mechanical processes associated with a complete MMR reaction remain enigmatic. The purified human (Homo sapien or Hs) 5'-MMR excision reaction requires the HsMSH2-HsMSH6 heterodimer, the 5' -> 3' exonuclease HsEXOI, and the single-stranded binding heterotrimer HsRPA. The HsMLH1-HsPMS2 heterodimer substantially influences 5'-MMR excision in cell extracts but is not required in the purified system. Using real-time single-molecule imaging, we show that HsRPA or Escherichia coli EcSSB restricts HsEXOI excision activity on nicked or gapped DNA. HsMSH2-HsMSH6 activates HsEXOI by overcoming HsRPA/EcSSB inhibition and exploits multiple dynamic sliding clamps to increase tract length. Conversely, HsMLH1-HsPMS2 regulates tract length by controlling the number of excision complexes, providing a link to 5' MMR.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/29994
- DOI
- 10.1073/PNAS.1523748113
- ISSN
- 0027-8424
- Article Type
- Article
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 113, no. 12, page. 3281 - 3286, 2016-03-22
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