PMID- 15138265
OWN - NLM
STAT- MEDLINE
DCOM- 20040817
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 29
DP  - 2004 Jul 16
TI  - Oxidative stress/damage induces multimerization and interaction of Fanconi anemia 
      proteins.
PG  - 30053-9
AB  - Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a 
      hypersensitivity to DNA-damaging agents, chromosomal instability, and defective 
      DNA repair. Eight FANC genes have been identified so far, and five of them 
      (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at 
      least in part in a complex to activate FANCD2 by monoubiquitination. Here we show 
      that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or 
      form a nuclear complex in response to oxidative stress/damage. Both FANCA and 
      FANCG proteins exist as monomers under non-oxidizing conditions, whereas they 
      become multimers following H2O2 treatment. Treatment of cells with oxidizing 
      agent not only triggers the multimeric complex of FANCA and FANCG in vivo but 
      also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment 
      abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken 
      together, our results lead us to conclude that FANCA and FANCG uniquely respond 
      to oxidative damage by forming complex(es) via intermolecular disulfide 
      linkage(s), which may be crucial in forming such complexes and in determining 
      their function.
FAU - Park, Su-Jung
AU  - Park SJ
AD  - Department of Biochemistry and Molecular Biology, Indiana University School of 
      Medicine, Indianapolis 46202, USA.
FAU - Ciccone, Samantha L M
AU  - Ciccone SL
FAU - Beck, Brian D
AU  - Beck BD
FAU - Hwang, Byounghoon
AU  - Hwang B
FAU - Freie, Brian
AU  - Freie B
FAU - Clapp, D Wade
AU  - Clapp DW
FAU - Lee, Suk-Hee
AU  - Lee SH
LA  - eng
GR  - CA92111/CA/NCI NIH HHS/United States
GR  - F32 GM20167-01/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040510
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Disulfides)
RN  - 0 (FANCA protein, human)
RN  - 0 (FANCG protein, human)
RN  - 0 (Fanconi Anemia Complementation Group A Protein)
RN  - 0 (Fanconi Anemia Complementation Group G Protein)
RN  - 0 (Oxidants)
RN  - 0 (Proteins)
RN  - 50SG953SK6 (Mitomycin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - O3C74ACM9V (Ethylmaleimide)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Cloning, Molecular
MH  - DNA Damage
MH  - DNA Repair
MH  - DNA, Complementary/metabolism
MH  - DNA-Binding Proteins/*physiology
MH  - Dimerization
MH  - Disulfides
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Ethylmaleimide/pharmacology
MH  - Fanconi Anemia/*metabolism
MH  - Fanconi Anemia Complementation Group A Protein
MH  - Fanconi Anemia Complementation Group G Protein
MH  - Glutathione Transferase/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen Peroxide/chemistry/pharmacology
MH  - Mitomycin/pharmacology
MH  - Models, Biological
MH  - Oxidants/pharmacology
MH  - Oxidation-Reduction
MH  - *Oxidative Stress
MH  - Oxygen/metabolism
MH  - Precipitin Tests
MH  - Protein Structure, Tertiary
MH  - Proteins/*physiology
EDAT- 2004/05/13 05:00
MHDA- 2004/08/18 05:00
CRDT- 2004/05/13 05:00
PHST- 2004/05/13 05:00 [pubmed]
PHST- 2004/08/18 05:00 [medline]
PHST- 2004/05/13 05:00 [entrez]
AID - S0021-9258(19)71015-1 [pii]
AID - 10.1074/jbc.M403527200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Jul 16;279(29):30053-9. doi: 10.1074/jbc.M403527200. Epub 2004 
      May 10.