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{{STRUCTURE_4ne5|  PDB=4ne5  |  SCENE=  }}
===Human MHF1-MHF2 complex===
{{ABSTRACT_PUBMED_24390579}}


==Function==
==Human MHF1-MHF2 complex==
[[http://www.uniprot.org/uniprot/CENPS_HUMAN CENPS_HUMAN]] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:8] [[http://www.uniprot.org/uniprot/CENPX_HUMAN CENPX_HUMAN]] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:6]
<StructureSection load='4ne5' size='340' side='right'caption='[[4ne5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ne5]] is a 8 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=4NE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NE5 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4ne5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ne5 OCA], [https://pdbe.org/4ne5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ne5 RCSB], [https://www.ebi.ac.uk/pdbsum/4ne5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ne5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CENPS_HUMAN CENPS_HUMAN] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:8]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The conserved MHF1-MHF2 (MHF) complex functions in the activation of the Fanconi anaemia pathway of the DNA damage response, in regulating homologous recombination, and in DNA replication fork maintenance. MHF facilitates the processing of multiple types of branched DNAs by the DNA translocase FANCM. Here we report the crystal structure of a human MHF-DNA complex that reveals the DNA-binding mode of MHF. The structure suggests that MHF prefers branched DNA over double-stranded DNA because it engages two duplex arms. Biochemical analyses verify that MHF preferentially engages DNA forks or various four-way junctions independent of the junction-site structure. Furthermore, genetic experiments provide evidence that the observed DNA-binding interface of MHF is important for cellular resistance to DNA damage. These results offer insights into how the MHF complex recognizes branched DNA and stimulates FANCM activity at such a structure to promote genome maintenance.


==About this Structure==
The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes.,Zhao Q, Saro D, Sachpatzidis A, Singh TR, Schlingman D, Zheng XF, Mack A, Tsai MS, Mochrie S, Regan L, Meetei AR, Sung P, Xiong Y Nat Commun. 2014 Jan 3;5:2987. doi: 10.1038/ncomms3987. PMID:24390579<ref>PMID:24390579</ref>
[[4ne5]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NE5 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<ref group="xtra">PMID:024390579</ref><references group="xtra"/><references/>
</div>
[[Category: Sachpatzidis, A.]]
<div class="pdbe-citations 4ne5" style="background-color:#fffaf0;"></div>
[[Category: Saro, D.]]
 
[[Category: Sung, P.]]
==See Also==
[[Category: Xiong, Y.]]
*[[Centromere protein 3D structure|Centromere protein 3D structure]]
[[Category: Zhao, Q.]]
== References ==
[[Category: Dna binding protein]]
<references/>
[[Category: Dna repair]]
__TOC__
[[Category: Fancm]]
</StructureSection>
[[Category: Fanconi anemia]]
[[Category: Homo sapiens]]
[[Category: Genome maintenance]]
[[Category: Large Structures]]
[[Category: Histone fold]]
[[Category: Sachpatzidis A]]
[[Category: Nucleus]]
[[Category: Saro D]]
[[Category: Sung P]]
[[Category: Xiong Y]]
[[Category: Zhao Q]]

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