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Lookup NU author(s): Dr Alexandra Solovyova, Professor Bernard Connolly
DNA mismatch repair (MMR) and very-short patch (VSP) repair are two pathways involved in the repair of T:G mismatches. To learn about competition and cooperation between these two repair pathways, we analyzed the physical and functional interaction between MutL and Vsr using biophysical and biochemical methods. Analytical ultracentrifugation reveals a nucleotide-dependent interaction between Vsr and the N-terminal domain of MutL. Using chemical crosslinking, we mapped the interaction site of MutL for Vsr to a region between the N-terminal domains similar to that described before for the interaction between MutL and the strand discrimination endonuclease MutH of the MMR system. Competition between MutH and Vsr for binding to MutL resulted in inhibition of the mismatch-provoked MutS- and MutL-dependent activation of MutH, which explains the mutagenic effect of Vsr overexpression. Cooperation between MMR and VSP repair was demonstrated by the stimulation of the Vsr endonuclease in a MutS-, MutL- and ATP-hydrolysis-dependent manner, in agreement with the enhancement of VSP repair by MutS and MutL in vivo. These data suggest a mobile MutS-MutL complex in MMR signalling, that leaves the DNA mismatch prior to, or at the time of, activation of downstream effector molecules such as Vsr or MutH.
Author(s): Heinze RJ, Giron-Monzon L, Solovyova A, Elliot SL, Geisler S, Cupples CG, Connolly BA, Friedhoff P
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 2009
Volume: 37
Issue: 13
Pages: 4453-4463
Date deposited: 06/04/2010
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/nar/gkp380
DOI: 10.1093/nar/gkp380
Notes: Journal article Nucleic acids research Nucleic Acids Res. 2009 May 27.
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