Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

Steven H. Wooden, Heather M. Bassett, Thomas Wood, Amanda K. McCullough

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Mutations found in human tumors often include transversions of GC to TA that may result from the mis-pairing of 8-oxoG with adenine during DNA replication. The human MutY (hMYH) enzyme, an adenine-specific DNA glycosylase, initiates repair at this mismatch. It has recently been demonstrated that inherited variants of hMYH may predispose individuals to multiple colorectal adenomas and carcinoma [Nat. Genet. 30 (2002) 227]. In this study, we demonstrate that two of these cancer-associated hMYH mutants, Y165C and G382D, are devoid of glycosylase activity directed towards 8-oxoG:A mispairs. These findings implicate a total loss of hMYH function associated with colorectal cancers.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalCancer Letters
Volume205
Issue number1
DOIs
StatePublished - Mar 8 2004

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Adenine
Colorectal Neoplasms
DNA Glycosylases
Viverridae
Mutation
DNA Mismatch Repair
DNA Replication
Adenoma
Neoplasms
Enzymes

Keywords

  • Cancer
  • Colorectal adenomas
  • DNA repair
  • MutY
  • Oxidative damage

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer. / Wooden, Steven H.; Bassett, Heather M.; Wood, Thomas; McCullough, Amanda K.

In: Cancer Letters, Vol. 205, No. 1, 08.03.2004, p. 89-95.

Research output: Contribution to journalArticle

Wooden, Steven H. ; Bassett, Heather M. ; Wood, Thomas ; McCullough, Amanda K. / Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer. In: Cancer Letters. 2004 ; Vol. 205, No. 1. pp. 89-95.
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