4MKY: Polymerase Domain From Mycobacterium Tuberculosis Ligase D In Complex With An Annealed Double-strand Dna Break

Citation:
Abstract
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.
PDB ID: 4MKYDownload
MMDB ID: 115894
PDB Deposition Date: 2013/9/5
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4MKY: hexameric; determined by author and by software (PISA)
Molecular Components in 4MKY
Label Count Molecule
Proteins (2 molecules)
2
DNA Ligase-like Protein Rv0938/mt0965
Molecule annotation
Nucleotides(2 molecules)
2
5'-d(p*dgp*dcp*dgp*dgp*dc)-3'
Molecule annotation
2
5'-d(*dgp*dcp*dcp*dgp*dcp*dap*dgp*dtp*dap*dc)-3'
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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