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Nirwal, Shivlee and Kulkarni, Dhananjaya S and Sharma, Amit and Rao, Desirazu N and Nair, Deepak T (2017) 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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The DNA mismatch repair (MMR) pathway removes errors that appear during genome replication. MutS is the primary mismatch sensor and forms an asym- metric 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 ori- gin 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 cen- tral tunnel. The comparison with structures of MutS– DNA complexes suggests that the mismatch scan- ning monomer (Bm) will move by nearly 50 A ̊ to as- sociate 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 pli- ers to bend DNA. We also shed light on the allosteric mechanism that influences the expulsion of adeno- sine triphosphate from Am on DNA binding. Overall, this study provides mechanistic insight regarding the primary event in MMR i.e. the assembly of the MutS– DNA complex.

Item Type: Article
Subjects: Biochemical and Biophysical Sciences
Depositing User: Dr Vengadesan Krishnan
Date Deposited: 30 Aug 2018 12:01
Last Modified: 30 Aug 2018 12:01
URI: http://rcb.sciencecentral.in/id/eprint/159

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