4ne3

Human MHF1-MHF2 complexHuman MHF1-MHF2 complex

Structural highlights

4ne3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8007Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] [REFERENCE:8]

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T. The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol. 2009 Jul 27;186(2):173-82. doi: 10.1083/jcb.200903100. Epub 2009 Jul, 20. PMID:19620631 doi:http://dx.doi.org/10.1083/jcb.200903100
↑ Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi:, 10.1073/pnas.1210303109. Epub 2012 Jul 18. PMID:22814378 doi:http://dx.doi.org/10.1073/pnas.1210303109
↑ 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. The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes. Nat Commun. 2014 Jan 3;5:2987. doi: 10.1038/ncomms3987. PMID:24390579 doi:http://dx.doi.org/10.1038/ncomms3987

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OCA

[1] Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T. The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol. 2009 Jul 27;186(2):173-82. doi: 10.1083/jcb.200903100. Epub 2009 Jul, 20. PMID:19620631 doi:http://dx.doi.org/10.1083/jcb.200903100

[2] Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi:, 10.1073/pnas.1210303109. Epub 2012 Jul 18. PMID:22814378 doi:http://dx.doi.org/10.1073/pnas.1210303109

[3] 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. The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes. Nat Commun. 2014 Jan 3;5:2987. doi: 10.1038/ncomms3987. PMID:24390579 doi:http://dx.doi.org/10.1038/ncomms3987

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