BIOMAT Database Logo BIOMAT Database Logo

Molecular basis for DNA double-strand break annealing and primer extension by an NHEJ DNA polymerase. 2013

Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.

Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break (DSB) repair pathways. The mechanisms by which breaks are competently brought together and extended during NHEJ is poorly understood. As polymerases extend DNA in a 5'-3' direction by nucleotide addition to a primer, it is unclear how NHEJ polymerases fill in break termini containing 3' overhangs that lack a primer strand. Here, we describe, at the molecular level, how prokaryotic NHEJ polymerases configure a primer-template substrate by annealing the 3' overhanging strands from opposing breaks, forming a gapped intermediate that can be extended in trans. We identify structural elements that facilitate docking of the 3' ends in the active sites of adjacent polymerases and reveal how the termini act as primers for extension of the annealed break, thus explaining how such DSBs are extended in trans. This study clarifies how polymerases couple break-synapsis to catalysis, providing a molecular mechanism to explain how primer extension is achieved on DNA breaks.

UI MeSH Term Description Entries
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D045643 DNA Repair Enzymes Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions. DNA Repair Enzyme,Enzyme, DNA Repair,Enzymes, DNA Repair,Repair Enzyme, DNA,Repair Enzymes, DNA
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D059766 DNA End-Joining Repair The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly. Non-Homologous DNA End-Joining,End-Joining DNA Repair,MMEJ DNA Repair,Microhomology-Mediated End Joining Repair,NHEJ DNA Repair,Nonhomologous DNA End-Joining,DNA End Joining Repair,DNA End-Joining, Non-Homologous,DNA End-Joining, Nonhomologous,DNA Repair, End-Joining,DNA Repair, MMEJ,DNA Repair, NHEJ,End Joining DNA Repair,End-Joining Repair, DNA,End-Joining, Non-Homologous DNA,Microhomology Mediated End Joining Repair,Non Homologous DNA End Joining,Nonhomologous DNA End Joining,Repair, DNA End-Joining,Repair, End-Joining DNA,Repair, MMEJ DNA,Repair, NHEJ DNA
D017931 DNA Primers Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques. DNA Primer,Oligodeoxyribonucleotide Primer,Oligodeoxyribonucleotide Primers,Oligonucleotide Primer,Oligonucleotide Primers,Primer, DNA,Primer, Oligodeoxyribonucleotide,Primer, Oligonucleotide,Primers, DNA,Primers, Oligodeoxyribonucleotide,Primers, Oligonucleotide
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

Related Publications

Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Multicomponent assemblies in DNA-double-strand break repair by NHEJ.
April 2019, Current opinion in structural biology,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Molecular basis for DNA strand displacement by NHEJ repair polymerases.
March 2016, Nucleic acids research,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange.
August 2018, Molecular cell,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway.
May 2008, Biochemical and biophysical research communications,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.
January 2003, Science (New York, N.Y.),
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
DNA polymerase θ (POLQ), double-strand break repair, and cancer.
August 2016, DNA repair,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Analysis of DNA Double-Strand Break End Resection and Single-Strand Annealing in S. pombe.
January 2021, Methods in molecular biology (Clifton, N.J.),
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Structural evidence for an in trans base selection mechanism involving Loop1 in polymerase μ at an NHEJ double-strand break junction.
July 2019, The Journal of biological chemistry,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons.
January 2006, Neuroscience letters,
Nigel C Brissett, and Maria J Martin, and Edward J Bartlett, and Julie Bianchi, and Luis Blanco, and Aidan J Doherty
Molecular mechanisms of DNA double strand break repair.
December 1998, Trends in cell biology,
Copied contents to your clipboard!