View source for 9bh9


==Human DNA polymerase theta helicase domain dimer bound to DNA in the microhomology aligning conformation==
<StructureSection load='9bh9' size='340' side='right'caption='[[9bh9]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bh9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BH9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#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=9bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bh9 OCA], [https://pdbe.org/9bh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bh9 RCSB], [https://www.ebi.ac.uk/pdbsum/9bh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bh9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPOLQ_HUMAN DPOLQ_HUMAN] Has a DNA polymerase activity on nicked double-stranded DNA and on a singly primed DNA template. The enzyme activity is resistant to aphidicolin, and inhibited by dideoxynucleotides. Exhibites a single-stranded DNA-dependent ATPase activity. Could be involved in the repair of interstrand cross-links.<ref>PMID:14576298</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA double-strand breaks occur daily in all human cells and must be repaired with high fidelity to minimize genomic instability. Deficiencies in high-fidelity DNA repair by homologous recombination lead to dependence on DNA polymerase theta, which identifies DNA microhomologies in 3' single-stranded DNA overhangs and anneals them to initiate error-prone double-strand break repair. The resulting genomic instability is associated with numerous cancers, thereby making this polymerase an attractive therapeutic target. However, despite the biomedical importance of polymerase theta, the molecular details of how it initiates DNA break repair remain unclear. Here, we present cryo-electron microscopy structures of the polymerase theta helicase domain bound to microhomology-containing DNA, revealing DNA-induced rearrangements of the helicase that enable DNA repair. Our structures show that DNA-bound helicase dimers facilitate a microhomology search that positions 3' single-stranded DNA ends in proximity to align complementary bases and anneal DNA microhomology. We characterize the molecular determinants that enable the helicase domain of polymerase theta to identify and pair DNA microhomologies to initiate mutagenic DNA repair, thereby providing insight into potentially targetable interactions for therapeutic interventions.

Human polymerase theta helicase positions DNA microhomologies for double-strand break repair.,Zerio CJ, Bai Y, Sosa-Alvarado BA, Guzi T, Lander GC Nat Struct Mol Biol. 2025 Feb 28. doi: 10.1038/s41594-025-01514-8. PMID:40021738<ref>PMID:40021738</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bh9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Lander GC]]
[[Category: Zerio CJ]]