9ask: Difference between revisions
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The | ==Human DNA polymerase theta helicase domain dimer, apo-form== | ||
<StructureSection load='9ask' size='340' side='right'caption='[[9ask]], [[Resolution|resolution]] 3.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ask]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ASK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ASK 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]] 3.6Å</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=9ask FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ask OCA], [https://pdbe.org/9ask PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ask RCSB], [https://www.ebi.ac.uk/pdbsum/9ask PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ask 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 (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Poltheta) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Poltheta is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Poltheta-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Poltheta helicase domain (Poltheta-hel) in complex with DNA containing different 3'-ssDNA overhangs. The structures reveal the sequential conformations adopted by Poltheta-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Poltheta-hel subdomains and its functional dimeric state are pivotal for aligning the 3'-ssDNA overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Poltheta-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Poltheta-hel. | |||
Structural basis for Poltheta-helicase DNA binding and microhomology-mediated end-joining.,Ito F, Li Z, Minakhin L, Khant HA, Pomerantz RT, Chen XS Nat Commun. 2025 Apr 19;16(1):3725. doi: 10.1038/s41467-025-58441-x. PMID:40253368<ref>PMID:40253368</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ask" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen XS]] | |||
[[Category: Ito F]] | |||
[[Category: Li Z]] | |||
