Variant base excision repair proteins: contributors to genomic instability.
Cells sustain endogenous DNA damage at rates greater than 20,000 DNA lesions per cell per day. These damages occur largely as a result of the inherently unstable nature of DNA and the presence of reactive oxygen species within cells. The base excision repair system removes the majority of DNA lesions resulting from endogenous DNA damage. There are several enzymes that function during base excision repair. Importantly, there are over 100 germline single nucleotide polymorphisms in genes that function in base excision repair and that result in non-synonymous amino acid substitutions in the proteins they encode. Somatic variants of these enzymes are also found in human tumors. Variant repair enzymes catalyze aberrant base excision repair. Aberrant base excision repair combined with continuous endogenous DNA damage over time has the potential to lead to a mutator phenotype. Mutations that arise in key growth control genes, imbalances in chromosome number, chromosomal translocations, and loss of heterozygosity can result in the initiation of human cancer or its progression.
Department of Therapeutic Radiology, 15 York Street, New Haven, CT 06510, United States.
Antonia A
AA
Nemec
Susan S
SS
Wallace
Joann B
JB
Sweasy
D019943:Amino Acid Substitution; D000818:Animals; D002869:Chromosome Aberrations; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins; D004259:DNA-Directed DNA Polymerase; D045647:DNA Glycosylases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus