PMID- 22510687
OWN - NLM
STAT- MEDLINE
DCOM- 20120726
LR  - 20211021
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 3
DP  - 2012 Apr 17
TI  - The structure of the FANCM-MHF complex reveals physical features for functional 
      assembly.
PG  - 782
LID - 10.1038/ncomms1779 [doi]
AB  - Fanconi anaemia is a rare genetic disease characterized by chromosomal 
      instability and cancer susceptibility. The Fanconi anaemia complementation group 
      protein M (FANCM) forms an evolutionarily conserved DNA-processing complex with 
      MHF1/MHF2 (histone-fold-containing proteins), which is essential for DNA repair 
      in response to genotoxic stress. Here we present the crystal structures of the 
      MHF1-MHF2 complex alone and bound to a fragment of FANCM (FANCM(661-800), 
      designated FANCM-F). The structures show that MHF1 and MHF2 form a compact 
      tetramer to which FANCM-F binds through a 'dual-V' shaped structure. FANCM-F and 
      (MHF1-MHF2)(2) cooperate to constitute a new DNA-binding site that is coupled to 
      the canonical L1L2 region. Perturbation of the MHF-FANCM-F structural plasticity 
      changes the localization of FANCM in vivo. The MHF-FANCM interaction and its 
      subcellular localization are altered by a disease-associated mutant of FANCM. 
      These findings reveal the molecular basis of MHF-FANCM recognition and provide 
      mechanistic insights into the pathway leading to Fanconi anaemia.
FAU - Tao, Yuyong
AU  - Tao Y
AD  - Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 
      230026, China.
FAU - Jin, Changjiang
AU  - Jin C
FAU - Li, Xu
AU  - Li X
FAU - Qi, Shali
AU  - Qi S
FAU - Chu, Lingluo
AU  - Chu L
FAU - Niu, Liwen
AU  - Niu L
FAU - Yao, Xuebiao
AU  - Yao X
FAU - Teng, Maikun
AU  - Teng M
LA  - eng
SI  - PDB/4DRA
SI  - PDB/4DRB
GR  - G12 RR003034/RR/NCRR NIH HHS/United States
GR  - U54 CA118948/CA/NCI NIH HHS/United States
GR  - CA118948/CA/NCI NIH HHS/United States
GR  - R01 DK056292/DK/NIDDK NIH HHS/United States
GR  - DK56292/DK/NIDDK NIH HHS/United States
GR  - R01 CA164133/CA/NCI NIH HHS/United States
GR  - S21 MD000101/MD/NIMHD NIH HHS/United States
GR  - 2G12RR003034-26/RR/NCRR NIH HHS/United States
GR  - R01 DK115812/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120417
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (CENPS protein, human)
RN  - 0 (CENPX protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.6.1.- (FANCM protein, human)
RN  - EC 3.6.4.- (DNA Helicases)
SB  - IM
MH  - Apoptosis Regulatory Proteins/*chemistry/genetics/*metabolism
MH  - Crystallography, X-Ray
MH  - DNA Helicases/*chemistry/genetics/*metabolism
MH  - DNA-Binding Proteins/*chemistry/genetics/*metabolism
MH  - Fanconi Anemia/metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Nuclear Proteins/*chemistry/genetics/*metabolism
MH  - Protein Binding
MH  - Tumor Suppressor Proteins/*chemistry/genetics/*metabolism
PMC - PMC3646547
MID - NIHMS425506
EDAT- 2012/04/19 06:00
MHDA- 2012/07/27 06:00
PMCR- 2013/05/07
CRDT- 2012/04/19 06:00
PHST- 2011/12/05 00:00 [received]
PHST- 2012/03/08 00:00 [accepted]
PHST- 2012/04/19 06:00 [entrez]
PHST- 2012/04/19 06:00 [pubmed]
PHST- 2012/07/27 06:00 [medline]
PHST- 2013/05/07 00:00 [pmc-release]
AID - ncomms1779 [pii]
AID - 10.1038/ncomms1779 [doi]
PST - epublish
SO  - Nat Commun. 2012 Apr 17;3:782. doi: 10.1038/ncomms1779.