Journal
MOLECULAR MICROBIOLOGY
Volume 87, Issue 3, Pages 553-568Publisher
WILEY
DOI: 10.1111/mmi.12115
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Funding
- Wendy Will Case Cancer Fund
- National Science Foundation [MCB 1050948, MCB 1022203]
- Direct For Biological Sciences [1050948] Funding Source: National Science Foundation
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1022203] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience [1050948] Funding Source: National Science Foundation
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Mismatch repair (MMR) increases the fidelity of DNA replication by identifying and correcting replication errors. Processivity clamps are vital components of DNA replication and MMR, yet the mechanism and extent to which they participate in MMR remains unclear. We investigated the role of the Bacillus subtilis processivity clamp DnaN, and found that it serves as a platform for mismatch detection and coupling of repair to DNA replication. By visualizing functional MutS fluorescent fusions in vivo, we find that MutS forms foci independent of mismatch detection at sites of replication (i.e. the replisome). These MutS foci are directed to the replisome by DnaN clamp zones that aid mismatch detection by targeting the search to nascent DNA. Following mismatch detection, MutS disengages from the replisome, facilitating repair. We tested the functional importance of DnaN-mediated mismatch detection for MMR, and found that it accounts for 90% of repair. This high dependence on DnaN can be bypassed by increasing MutS concentration within the cell, indicating a secondary mode of detection in vivo whereby MutS directly finds mismatches without associating with the replisome. Overall, our results provide new insight into the mechanism by which DnaN couples mismatch recognition to DNA replication in living cells.
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