DnaN clamp zones provide a platform for spatiotemporal coupling of mismatch detection to DNA replication. Issue 3 (11th December 2012)

• Record Type: Journal Article
• Authors: Lenhart, Justin S.; Sharma, Anushi; Hingorani, Manju M.; Simmons, Lyle A.
• Is Part Of: Molecular microbiology. Volume 87:Issue 3(2013)
• Page Start: 553
• Page End: 568
• Publication Date: 2012-12-11
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12115
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>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 <italic>Bacillus subtilis</italic> 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 <italic>in vivo</italic>, 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 <italic>in vivo</italic> 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.</p> </abstract>