Repair of 8-oxoG: A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine

Douglas M. Banda, Nicole N. Nuñez, Michael A. Burnside, Katie M. Bradshaw, Sheila S. David

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome. The paramount role of MUTYH in guarding the genome is well established in the etiology of a colorectal cancer predisposition syndrome involving variants of MUTYH, referred to as MUTYH-associated polyposis (MAP). In this review, we highlight recent advances in understanding how MUTYH structure and related function participate in the manifestation of human disease such as MAP. Here we focus on the importance of MUTYH's metal cofactor sites, including a recently discovered "Zinc linchpin" motif, as well as updates to the catalytic mechanism. Finally, we touch on the insight gleaned from studies with MAP-associated MUTYH variants and recent advances in understanding the multifaceted roles of MUTYH in the cell, both in the prevention of mutagenesis and tumorigenesis.

Original languageEnglish (US)
JournalFree Radical Biology and Medicine
DOIs
StateAccepted/In press - Nov 17 2016

Fingerprint

Medicine
Repair
Metals
Reactive Nitrogen Species
DNA
DNA Repair
Reactive Oxygen Species
Genome
DNA Glycosylases
Genes
Adenine
Eukaryota
Mutagenesis
Zinc
Colorectal Neoplasms
Carcinogenesis
Sugars
Mutation
8-hydroxyguanine
Proteins

Keywords

  • 8-oxoguanine
  • Base excision repair
  • Fe-S clusters
  • Glycosylase
  • MutY
  • MUTYH
  • MUTYH-associated polyposis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Repair of 8-oxoG : A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine. / Banda, Douglas M.; Nuñez, Nicole N.; Burnside, Michael A.; Bradshaw, Katie M.; David, Sheila S.

In: Free Radical Biology and Medicine, 17.11.2016.

Research output: Contribution to journalArticle

Banda, Douglas M. ; Nuñez, Nicole N. ; Burnside, Michael A. ; Bradshaw, Katie M. ; David, Sheila S. / Repair of 8-oxoG : A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine. In: Free Radical Biology and Medicine. 2016.
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