Mechanism of formation of a toroid around DNA by the mismatch sensor protein

Nirwal, Shivlee (2018) Mechanism of formation of a toroid around DNA by the mismatch sensor protein. Nucleic Acids Research, 46 (1). pp. 256-266. ISSN 0305-1048

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Abstract

The DNA mismatch repair (MMR) pathway removes errors that appear during genome replication. MutS is the primary mismatch sensor and forms an asymmetric dimer that encircles DNA to bend it to scan for mismatches. The mechanism utilized to load DNA into the central tunnel was unknown and the origin of the force required to bend DNA was unclear.We show that, in absence of DNA, MutS forms a symmetric dimer wherein a gap exists between the monomers through which DNA can enter the central tunnel. The comparison with structures of MutS–DNA complexessuggests that the mismatch scanning monomer (Bm) will move by nearly 50 °A to associate with the other monomer (Am). Consequently,the N-terminal domains of both monomers will press onto DNA to bend it. The proposed mechanism of toroid formation evinces that the force required to bend DNA arises primarily due to the movement of Bm and hence, the MutS dimer acts like a pair of pliers to bend DNA. We also shed light on the allosteric mechanism that influences the expulsion of adenosine triphosphate from Am on DNA binding. Overall,this study providesmechanistic insight regarding the primary event in MMR i.e. the assembly of the MutS–DNA complex.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 07 Feb 2019 09:02
Last Modified: 07 Feb 2019 09:02
URI: http://eprints.manipal.edu/id/eprint/153203

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