The beta sliding clamp binds to multiple sites within MutL and MutS - PubMed (original) (raw)

. 2006 May 19;281(20):14340-9.

doi: 10.1074/jbc.M601264200. Epub 2006 Mar 16.

Affiliations

• PMID: 16546997
• DOI: 10.1074/jbc.M601264200

Free article

The beta sliding clamp binds to multiple sites within MutL and MutS

Francisco J López de Saro et al. J Biol Chem. 2006.

Free article

Abstract

The MutL and MutS proteins are the central components of the DNA repair machinery that corrects mismatches generated by DNA polymerases during synthesis. We find that MutL interacts directly with the beta sliding clamp, a ring-shaped dimeric protein that confers processivity to DNA polymerases by tethering them to their substrates. Interestingly, the interaction of MutL with beta only occurs in the presence of single-stranded DNA. We find that the interaction occurs via a loop in MutL near the ATP-binding site. The binding site of MutL on beta locates to the hydrophobic pocket between domains two and three of the clamp. Site-specific replacement of two residues in MutL diminished interaction with beta without disrupting MutL function with helicase II. In vivo studies reveal that this mutant MutL is no longer functional in mismatch repair. In addition, the human MLH1 has a close match to the proliferating cell nuclear antigen clamp binding motif in the region that corresponds to the beta interaction site in Escherichia coli MutL, and a peptide corresponding to this site binds proliferating cell nuclear antigen. The current report also examines in detail the interaction of beta with MutS. We find that two distinct regions of MutS interact with beta. One is located near the C terminus and the other is close to the N terminus, within the mismatch binding domain. Complementation studies using genes encoding different MutS mutants reveal that the N-terminal beta interaction motif on MutS is essential for activity in vivo, but the C-terminal interaction site for beta is not. In light of these results, we propose roles for the beta clamp in orchestrating the sequence of events that lead to mismatch repair in the cell.

PubMed Disclaimer

Similar articles

• MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.
  Groothuizen FS, Winkler I, Cristóvão M, Fish A, Winterwerp HH, Reumer A, Marx AD, Hermans N, Nicholls RA, Murshudov GN, Lebbink JH, Friedhoff P, Sixma TK. Groothuizen FS, et al. Elife. 2015 Jul 11;4:e06744. doi: 10.7554/eLife.06744. Elife. 2015. PMID: 26163658 Free PMC article.
• The endonuclease domain of MutL interacts with the β sliding clamp.
  Pillon MC, Miller JH, Guarné A. Pillon MC, et al. DNA Repair (Amst). 2011 Jan 2;10(1):87-93. doi: 10.1016/j.dnarep.2010.10.003. Epub 2010 Nov 2. DNA Repair (Amst). 2011. PMID: 21050827 Free PMC article.
• A conserved MutS homolog connector domain interface interacts with MutL homologs.
  Mendillo ML, Hargreaves VV, Jamison JW, Mo AO, Li S, Putnam CD, Woods VL Jr, Kolodner RD. Mendillo ML, et al. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22223-8. doi: 10.1073/pnas.0912250106. Epub 2009 Dec 22. Proc Natl Acad Sci U S A. 2009. PMID: 20080788 Free PMC article.
• [Homologs of MutS and MutL during mammalian meiosis].
  Santucci-Darmanin S, Paquis-Flucklinger V. Santucci-Darmanin S, et al. Med Sci (Paris). 2003 Jan;19(1):85-91. doi: 10.1051/medsci/200319185. Med Sci (Paris). 2003. PMID: 12836196 Review. French.
• Structure and function of mismatch repair proteins.
  Yang W. Yang W. Mutat Res. 2000 Aug 30;460(3-4):245-56. doi: 10.1016/s0921-8777(00)00030-6. Mutat Res. 2000. PMID: 10946232 Review.

Cited by

• Coupling distant sites in DNA during DNA mismatch repair.
  Kolodner RD, Mendillo ML, Putnam CD. Kolodner RD, et al. Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):12953-4. doi: 10.1073/pnas.0705698104. Epub 2007 Jul 30. Proc Natl Acad Sci U S A. 2007. PMID: 17664420 Free PMC article. No abstract available.
• The frequency and structure of recombinant products is determined by the cellular level of MutL.
  Elez M, Radman M, Matic I. Elez M, et al. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8935-40. doi: 10.1073/pnas.0610149104. Epub 2007 May 14. Proc Natl Acad Sci U S A. 2007. PMID: 17502621 Free PMC article.
• The methylation-independent mismatch repair machinery in Pseudomonas aeruginosa.
  On YY, Welch M. On YY, et al. Microbiology (Reading). 2021 Dec;167(12):001120. doi: 10.1099/mic.0.001120. Microbiology (Reading). 2021. PMID: 34882086 Free PMC article. Review.
• Coordinating DNA polymerase traffic during high and low fidelity synthesis.
  Sutton MD. Sutton MD. Biochim Biophys Acta. 2010 May;1804(5):1167-79. doi: 10.1016/j.bbapap.2009.06.010. Epub 2009 Jun 21. Biochim Biophys Acta. 2010. PMID: 19540941 Free PMC article. Review.
• Quantitative transcription factor binding kinetics at the single-molecule level.
  Wang Y, Guo L, Golding I, Cox EC, Ong NP. Wang Y, et al. Biophys J. 2009 Jan;96(2):609-20. doi: 10.1016/j.bpj.2008.09.040. Biophys J. 2009. PMID: 19167308 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • BioCyc