Is base excision repair a tumor suppressor mechanism?
The base excision repair pathway is critical for the removal of oxidized and methylated bases from the DNA. Much of this DNA damage arises endogenously, as a result of oxygen metabolism. Several proteins including DNA glycosylases, the APE1 endonuclease, DNA polymerase beta and DNA ligase, act in a highly regulated and coordinated manner during base excision repair to excise the base adducts from the DNA and restore the normal DNA sequence. Both germline and tumor-associated variants of genes encoding these proteins have been identified in humans. In many cases, the protein variant has been shown to have properties that could contribute to the development of cancer, suggesting that base excision repair acts as a tumor suppressor mechanism in humans. Limited epidemiological studies are consistent with this view. Our review of the literature indicates that additional laboratory and epidemiological studies of the role of base excision repair in cancer etiology is warranted.
Sweasy
Joann B
JB
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. joann.sweasy@yale.edu
Lang
Tieming
T
DiMaio
Daniel
D
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D019951:DNA Polymerase beta; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase