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Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct.

Publication ,  Journal Article
Duckett, DR; Drummond, JT; Murchie, AI; Reardon, JT; Sancar, A; Lilley, DM; Modrich, P
Published in: Proc Natl Acad Sci U S A
June 25, 1996

Bacterial and mammalian mismatch repair systems have been implicated in the cellular response to certain types of DNA damage, and genetic defects in this pathway are known to confer resistance to the cytotoxic effects of DNA-methylating agents. Such observations suggest that in addition to their ability to recognize DNA base-pairing errors, members of the MutS family may also respond to genetic lesions produced by DNA damage. We show that the human mismatch recognition activity MutSalpha recognizes several types of DNA lesion including the 1,2-intrastrand d(GpG) crosslink produced by cis-diamminedichloroplatinum(II), as well as base pairs between O6-methylguanine and thymine or cytosine, or between O4-methylthymine and adenine. However, the protein fails to recognize 1,3-intrastrand adduct produced by trans-diamminedichloroplatinum(II) at a d(GpTpG) sequence. These observations imply direct involvement of the mismatch repair system in the cytotoxic effects of DNA-methylating agents and suggest that recognition of 1,2-intrastrand cis-diamminedichloroplatinum(II) adducts by MutSalpha may be involved in the cytotoxic action of this chemotherapeutic agent.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 25, 1996

Volume

93

Issue

13

Start / End Page

6443 / 6447

Location

United States

Related Subject Headings

  • Thymine
  • Protein Binding
  • MutS DNA Mismatch-Binding Protein
  • Molecular Sequence Data
  • Humans
  • Guanine
  • Escherichia coli Proteins
  • Dinucleoside Phosphates
  • DNA-Binding Proteins
  • DNA Repair
 

Citation

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Duckett, D. R., Drummond, J. T., Murchie, A. I., Reardon, J. T., Sancar, A., Lilley, D. M., & Modrich, P. (1996). Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc Natl Acad Sci U S A, 93(13), 6443–6447. https://doi.org/10.1073/pnas.93.13.6443
Duckett, D. R., J. T. Drummond, A. I. Murchie, J. T. Reardon, A. Sancar, D. M. Lilley, and P. Modrich. “Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct.Proc Natl Acad Sci U S A 93, no. 13 (June 25, 1996): 6443–47. https://doi.org/10.1073/pnas.93.13.6443.
Duckett DR, Drummond JT, Murchie AI, Reardon JT, Sancar A, Lilley DM, et al. Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6443–7.
Duckett, D. R., et al. “Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct.Proc Natl Acad Sci U S A, vol. 93, no. 13, June 1996, pp. 6443–47. Pubmed, doi:10.1073/pnas.93.13.6443.
Duckett DR, Drummond JT, Murchie AI, Reardon JT, Sancar A, Lilley DM, Modrich P. Human MutSalpha recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6443–6447.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 25, 1996

Volume

93

Issue

13

Start / End Page

6443 / 6447

Location

United States

Related Subject Headings

  • Thymine
  • Protein Binding
  • MutS DNA Mismatch-Binding Protein
  • Molecular Sequence Data
  • Humans
  • Guanine
  • Escherichia coli Proteins
  • Dinucleoside Phosphates
  • DNA-Binding Proteins
  • DNA Repair