View source for 4mky


==Polymerase Domain from Mycobacterium tuberculosis Ligase D in complex with an annealed double-strand DNA break.==
<StructureSection load='4mky' size='340' side='right'caption='[[4mky]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mky]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MKY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mky OCA], [https://pdbe.org/4mky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mky RCSB], [https://www.ebi.ac.uk/pdbsum/4mky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mky ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIGD_MYCTU LIGD_MYCTU] With Ku forms a non-homologous end joining (NHEJ) repair enzyme which repairs DNA double-strand breaks (DSB) with reduced fidelity. Recognizes, processes and reseals DSBs, including repairs on incompatible DSB which require 3'-resection, gap filling and ligation. Anneals the 3' overhanging strands from opposing breaks to form a gapped intermediate, which then can be extended in trans by using the termini as primers for extension of the annealed break. Binds to the recessed 5'-phosphate moiety of the downstream DNA strand forming a stable synaptic complex even when the 3'-protruding ends of the template DNA strands are not complementary. Has numerous activities; gap filling copies the template strand, and prefers a 5'-phosphate in the gap and rNTPS (PubMed:17174332, PubMed:17947582), DNA-directed DNA or RNA polymerase on 5'-overhangs, terminal transferase (extending ssDNA or blunt dsDNA in a non-templated fashion, preferentially with rNTPs), DNA-dependent RNA primase (synthesizes short RNAs on unprimed closed ssDNA) and 3'- to 5'-exonuclease on ssDNA (PubMed:15499016). Isolated Pol domain (and presumably the holoenzyme) is able to form complexes between 2 noncompatible protruding 3'-ends DNA ends via microhomologous DNA strands, in a end-bridging function to which it adds a templated nucleotide (PubMed:17947582). Minimal primer length is 2 nucleotides (PubMed:21255731).<ref>PMID:15499016</ref> <ref>PMID:17174332</ref> <ref>PMID:17947582</ref> <ref>PMID:21255731</ref>   The preference of the polymerase domain for rNTPs over dNTPs may be advantageous in dormant cells, where the dNTP pool is limiting.  In conjunction with endogenous or Mycobacterium phage Omega Ku (AC Q853W0) can reconstitute NHEJ in Saccharomyces cerevisiae.
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== Publication Abstract from PubMed ==
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.

Molecular Basis for DNA Double-Strand Break Annealing and Primer Extension by an NHEJ DNA Polymerase.,Brissett NC, Martin MJ, Bartlett EJ, Bianchi J, Blanco L, Doherty AJ Cell Rep. 2013 Nov 27;5(4):1108-20. doi: 10.1016/j.celrep.2013.10.016. Epub 2013 , Nov 14. PMID:24239356<ref>PMID:24239356</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4mky" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA ligase 3D structures|DNA ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Brissett NC]]
[[Category: Doherty AJ]]