Human MutY: Gene structure, protein functions and interactions, and role in carcinogenesis

A. R. Parker, J. R. Eshleman

Research output: Contribution to journalReview article

Abstract

Faithful maintenance of the genome is crucial to the individual and the species. Oxidative DNA dam age, such as 8-oxo-7,8-dihydroguanine (8-oxoG), poses a major threat to genomic integrity. 8-OxoG can mispair wth 2′-deoxycytidine 5′-triphosphate or with 2′-deoxyadenosine triphosphate during DNA replication, forming C•8-oxoG and A•8-oxoG mispairs. Human MutY is responsible for recognition and removal of the inappropriately inserted adenine in an A•8-oxoG mispair. If unrepaired, the A•8-oxoG mispairs can result in deleterious C:G to A:T transversions. Human MutY functions in a postreplication repair pathway and is targeted to the newly synthesized daughter strand of DNA for removal of the adenine base. The human MutY protein is targeted to both the mitochondria and the nucleus and associates with the proliferating cell nuclear antigen, apurinic/apyrimidinic endonuclease 1, replication protein A and mutS homolog 6 proteins. Mutations in the human MutY gene and defective activity of the human MutY protein have been detected in cancer. A direct correlation between defective A•8-oxoG repair and increased levels of genomic 8-oxoG has now been established.

Original languageEnglish (US)
Pages (from-to)2064-2083
Number of pages20
JournalCellular and Molecular Life Sciences
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2003

Keywords

  • 8-oxo-7,8-dihydroguanine
  • Base excision repair
  • Colorectal cancer
  • DNA repair
  • Genomic instability
  • Human MutY
  • hMYH

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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