MutL sliding clamps coordinate exonuclease-independent Escherichia coli mismatch repair
Jiaquan Liu,
Ryanggeun Lee,
Brooke M. Britton,
James A. London,
Keunsang Yang,
Jeungphill Hanne,
Jong-Bong Lee () and
Richard Fishel ()
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Jiaquan Liu: The Ohio State University Wexner Medical Center
Ryanggeun Lee: Pohang University of Science and Technology (POSTECH)
Brooke M. Britton: The Ohio State University Wexner Medical Center
James A. London: The Ohio State University Wexner Medical Center
Keunsang Yang: School of Interdisciplinary Bioscience and Bioengineering, POSTECH
Jeungphill Hanne: The Ohio State University Wexner Medical Center
Jong-Bong Lee: Pohang University of Science and Technology (POSTECH)
Richard Fishel: The Ohio State University Wexner Medical Center
Nature Communications, 2019, vol. 10, issue 1, 1-15
Abstract:
Abstract A shared paradigm of mismatch repair (MMR) across biology depicts extensive exonuclease-driven strand-specific excision that begins at a distant single-stranded DNA (ssDNA) break and proceeds back past the mismatched nucleotides. Historical reconstitution studies concluded that Escherichia coli (Ec) MMR employed EcMutS, EcMutL, EcMutH, EcUvrD, EcSSB and one of four ssDNA exonucleases to accomplish excision. Recent single-molecule images demonstrated that EcMutS and EcMutL formed cascading sliding clamps on a mismatched DNA that together assisted EcMutH in introducing ssDNA breaks at distant newly replicated GATC sites. Here we visualize the complete strand-specific excision process and find that long-lived EcMutL sliding clamps capture EcUvrD helicase near the ssDNA break, significantly increasing its unwinding processivity. EcSSB modulates the EcMutL–EcUvrD unwinding dynamics, which is rarely accompanied by extensive ssDNA exonuclease digestion. Together these observations are consistent with an exonuclease-independent MMR strand excision mechanism that relies on EcMutL–EcUvrD helicase-driven displacement of ssDNA segments between adjacent EcMutH–GATC incisions.
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13191-5
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DOI: 10.1038/s41467-019-13191-5
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