Targeting base excision repair to improve cancer therapies.
Most commonly used cancer therapies, particularly ionizing radiation and certain classes of cytotoxic chemotherapies, cause cell death by damaging DNA. Base excision repair (BER) is the major system responsible for the removal of corrupt DNA bases and repair of DNA single strand breaks generated spontaneously and induced by exogenous DNA damaging factors such as certain cancer therapies. In this review, the physico-chemical properties of the proteins involved in BER are discussed with particular emphasis on molecular mechanisms coordinating repair processes. The aim of this review is to apply extensive knowledge that currently exists regarding the biochemical mechanisms involved in human BER to the molecular biology of current therapies for cancer. It is anticipated that the application of this knowledge will translate into the development of novel effective therapies for improving existing treatments such as radiation therapy and oxaliplatin chemotherapy.
Sharma
Ricky A
RA
Radiation Oncology & Biology, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Dianov
Grigory L
GL
D000970:Antineoplastic Agents / Q000378:metabolism; D024161:Collagen Type XI / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D009687:Nuclear Proteins / Q000378:metabolism; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
C438188:APTX protein, human; D000970:Antineoplastic Agents; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D011116:Polynucleotide 5'-Hydroxyl-Kinase; D004259:DNA-Directed DNA Polymerase; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases