BRCT domain of DNA polymerase μ has DNA-binding activity and promotes the DNA polymerization activity

Genes Cells. 2012 Sep;17(9):790-806. doi: 10.1111/j.1365-2443.2012.01628.x. Epub 2012 Aug 16.


DNA polymerase μ (pol μ) catalyzes nonhomologous end-joining in DNA double-stranded break repair. Pol μ consists of an amino-terminal BRCA1 carboxyl-terminal homology (BRCT) domain and a pol β-like region, which contains the catalytic site. By DNA cellulose column chromatography, using full-length pol μ and five different deletion mutants, we found that the amino-terminal region has double-stranded DNA (dsDNA)-binding activity. Pol μ without BRCT domain reduces the DNA polymerization activity when compared to full-length pol μ. Observation by atomic force microscopy showed that full-length pol μ binds to the ends and middle part of dsDNA. Pol μ lacking the amino-terminal region or with a mutation within the BRCT domain bound only to DNA ends, whereas the amino-terminal region with the BRCT domain bound to both the ends and the middle part of dsDNA (mpdDNA). Terminal deoxynucleotidyltransferase, which, like pol μ, belongs to the X family DNA polymerases, also bound to mpdDNA through its amino-terminal region.

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Chromatography / methods
  • Cloning, Molecular
  • DNA / genetics
  • DNA / metabolism*
  • DNA Nucleotidylexotransferase / genetics
  • DNA Nucleotidylexotransferase / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Enzyme Activation
  • Gene Library
  • Genome, Human
  • Humans
  • Microscopy, Atomic Force
  • Mutation
  • Polymerization*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship


  • DNA-Binding Proteins
  • DNA
  • DNA polymerase mu
  • DNA Nucleotidylexotransferase
  • DNA-Directed DNA Polymerase