Genomes and Genes
fanconi anemia complementation group proteins
Summary: A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.
- Qiao F, Moss A, Kupfer G. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner. J Biol Chem. 2001;276:23391-6 pubmed..Furthermore, phosphorylation of FancG was found to be temporally correlated with exit of the FA complex from chromosomes at mitosis. Taken together, these findings suggest a role for FA proteins in chromatin and nuclear matrix. ..
- Paeschke K, McDonald K, Zakian V. Telomeres: structures in need of unwinding. FEBS Lett. 2010;584:3760-72 pubmed publisher..We summarize data showing that perturbation of their telomere activities can lead to telomere dysfunction and genome instability and in some cases human disease. ..
- Medhurst A, Huber P, Waisfisz Q, de Winter J, Mathew C. Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Hum Mol Genet. 2001;10:423-9 pubmed..These proteins may act either as a multimeric complex or by sequential recruitment of subsets of the proteins in a common pathway that protects the genomic integrity of mammalian cells. ..
- Wu Y, Sommers J, Suhasini A, Leonard T, Deakyne J, Mazin A, et al. Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes. Blood. 2010;116:3780-91 pubmed publisher..The ability of FANCJ to use the energy from ATP hydrolysis to produce the force required to unwind DNA or destabilize protein bound to DNA is required for its role in DNA repair. ..
- Nadler J, Braun R. Fanconi anemia complementation group C is required for proliferation of murine primordial germ cells. Genesis. 2000;27:117-23 pubmed..This study demonstrates Fancc is required for mitotic proliferation of primordial germ cells. ..
- Bharti S, Sommers J, George F, Kuper J, Hamon F, Shin ya K, et al. Specialization among iron-sulfur cluster helicases to resolve G-quadruplex DNA structures that threaten genomic stability. J Biol Chem. 2013;288:28217-29 pubmed publisher..These findings suggest FANCJ is a specialized Fe-S cluster helicase that preserves chromosomal stability by unwinding unimolecular G4 DNA likely to form in transiently unwound single-stranded genomic regions. ..
- Meng D, Wang X, Chang Q, Hitron A, Zhang Z, Xu M, et al. Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism. Toxicol Appl Pharmacol. 2010;244:291-9 pubmed publisher..These findings demonstrate a role for HO-1 in arsenite-mediated angiogenesis in vitro. ..
- Kim J, Kee Y, Gurtan A, D Andrea A. Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24. Blood. 2008;111:5215-22 pubmed publisher..Dysregulated loading of the FA core complex accounts, at least in part, for the characteristic cellular and developmental abnormalities in FA. ..
- Thompson L, Hinz J. Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights. Mutat Res. 2009;668:54-72 pubmed publisher..The FANCJ/BRIP1/BACH1 helicase functions in association with BRCA1 and may remove structural barriers to replication, such as guanine quadruplex structures, and/or assist in crosslink unhooking. ..
- Alpi A, Pace P, Babu M, Patel K. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008;32:767-77 pubmed publisher..This work therefore establishes a system that provides mechanistic insight into the functions of FANCL and FANCI in the catalysis of FANCD2 monoubiquitination. ..
- Ishiai M, Kitao H, Smogorzewska A, Tomida J, Kinomura A, Uchida E, et al. FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Nat Struct Mol Biol. 2008;15:1138-46 pubmed publisher..Mutational analysis of putative phosphorylation sites in human FANCI indicates that this switch is evolutionarily conserved. ..
- Wang W. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet. 2007;8:735-48 pubmed..Now that the gene that is defective in the thirteenth and last assigned FA complementation group (FANCI) has been identified, I discuss what is known about FA proteins and their interactive network, and what remains to be discovered. ..
- Du Z, Hu L, Wang H, Yan L, Zeng Y, Shao J, et al. Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS ONE. 2011;6:e19137 pubmed publisher..The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated...
- Gupta R, Sharma S, Sommers J, Jin Z, Cantor S, Brosh R. Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer. J Biol Chem. 2005;280:25450-60 pubmed
- Hadjur S, Ung K, Wadsworth L, Dimmick J, Rajcan Separovic E, Scott R, et al. Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase. Blood. 2001;98:1003-11 pubmed..These results suggested that the altered redox state likely present in Fancc(-/-) Sod1(-/-) hematopoietic progenitors was responsible for an impairment of cell proliferation or survival. (Blood. 2001;98:1003-1011) ..
- Taniguchi T, D Andrea A. The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Blood. 2002;100:2457-62 pubmed..Our data indicate that FANCE is a component of the nuclear FA complex in vivo and is required for the monoubiquitination of FANCD2 and the downstream events in the FA pathway. ..
- Kanezaki R, Toki T, Yokoyama M, Yomogida K, Sugiyama K, Yamamoto M, et al. Transcription factor BACH1 is recruited to the nucleus by its novel alternative spliced isoform. J Biol Chem. 2001;276:7278-84 pubmed..These results suggested that BACH1t recruits BACH1 to the nucleus through BTB domain-mediated interaction. ..
- Freie B, Li X, Ciccone S, Nawa K, Cooper S, Vogelweid C, et al. Fanconi anemia type C and p53 cooperate in apoptosis and tumorigenesis. Blood. 2003;102:4146-52 pubmed..Collectively, these data demonstrate that p53 and Fancc interact functionally to regulate apoptosis and tumorigenesis in Fancc-deficient cells. ..
- de Winter J, van Der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, et al. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet. 2000;9:2665-74 pubmed..Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity. ..
- Zanier R, Briot D, Dugas du Villard J, Sarasin A, Rosselli F. Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation. Oncogene. 2004;23:5004-13 pubmed..The potential role of the differentially expressed genes in FA phenotype as well as a functional- and cellular-based clustering of the identified genes are presented and discussed. ..
- Xie J, Litman R, Wang S, Peng M, Guillemette S, Rooney T, et al. Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Oncogene. 2010;29:2499-508 pubmed publisher..Moreover, unregulated FANCJ function could be associated with cancer and/or chemoresistance. ..
- Hiom K. FANCJ: solving problems in DNA replication. DNA Repair (Amst). 2010;9:250-6 pubmed publisher..Here I will discuss the contribution of FANCJ to human disease, its role in maintenance of genome stability and some current thoughts on the mechanisms through which this is achieved. ..
- Pace P, Johnson M, Tan W, Mosedale G, Sng C, Hoatlin M, et al. FANCE: the link between Fanconi anaemia complex assembly and activity. EMBO J. 2002;21:3414-23 pubmed..Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage. ..
- Shen X, Do H, Li Y, Chung W, Tomasz M, de Winter J, et al. Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication. Mol Cell. 2009;35:716-23 pubmed publisher..Thus, FA proteins participate in distinct DNA damage response mechanisms governed by DNA replication status. ..
- Vinciguerra P, Godinho S, Parmar K, Pellman D, D Andrea A. Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells. J Clin Invest. 2010;120:3834-42 pubmed publisher..Based on these observations, we suggest that cytokinesis failure followed by apoptosis may contribute to bone marrow failure in patients with FA. ..
- Palle K, Vaziri C. Rad18 E3 ubiquitin ligase activity mediates Fanconi anemia pathway activation and cell survival following DNA Topoisomerase 1 inhibition. Cell Cycle. 2011;10:1625-38 pubmed
- Botuyan M, Nominé Y, Yu X, Juranic N, Macura S, Chen J, et al. Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains. Structure. 2004;12:1137-46 pubmed
- Tahara T, Sun J, Igarashi K, Taketani S. Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells. Biochem Biophys Res Commun. 2004;324:77-85 pubmed..These results indicated that heme plays an important role in the induction of alpha-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells. ..
- Shan Y, Lambrecht R, Ghaziani T, Donohue S, Bonkovsky H. Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells: insights from studies with small interfering RNAS. J Biol Chem. 2004;279:51769-74 pubmed..Exogenous heme produces additional up-regulation, beyond that produced by Bach-1 siRNAs, suggesting that heme does not act solely through its effects on Bach-1. ..
- Sareen A, Chaudhury I, Adams N, Sobeck A. Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase. Nucleic Acids Res. 2012;40:8425-39 pubmed publisher..Moreover, the concentration of chromatin-bound FANCD2 exceeds that of FANCI throughout replication. Our results suggest that FANCD2 and FANCI function separately at consecutive steps during DNA repair in S-phase...
- Sato K, Ishiai M, Toda K, Furukoshi S, Osakabe A, Tachiwana H, et al. Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair. EMBO J. 2012;31:3524-36 pubmed publisher..Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair. ..
- Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald E, Hurov K, Luo J, et al. Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell. 2007;129:289-301 pubmed..Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I. ..
- Noda T, Takahashi A, Kondo N, Mori E, Okamoto N, Nakagawa Y, et al. Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage. Biochem Biophys Res Commun. 2011;404:206-10 pubmed publisher..These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. ..
- Garcia Higuera I, Taniguchi T, Ganesan S, Meyn M, Timmers C, Hejna J, et al. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol Cell. 2001;7:249-62 pubmed..The FANCD2 protein, therefore, provides the missing link between the FA protein complex and the cellular BRCA1 repair machinery. Disruption of this pathway results in the cellular and clinical phenotype common to all FA subtypes. ..
- Mosedale G, Niedzwiedz W, Alpi A, Perrina F, Pereira Leal J, Johnson M, et al. The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway. Nat Struct Mol Biol. 2005;12:763-71 pubmed..This discovery sheds light on the origins, regulation and molecular function of the FA tumor-suppressor pathway in the maintenance of genome stability. ..
- Kupfer G, Yamashita T, Naf D, Suliman A, Asano S, D Andrea A. The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2. Blood. 1997;90:1047-54 pubmed..Absence of a functional interaction between FAC and cdc2 in FA cells may underlie the cell cycle abnormality and clinical abnormalities of FA. ..
- Knipscheer P, Raschle M, Smogorzewska A, Enoiu M, Ho T, SCHARER O, et al. The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science. 2009;326:1698-701 pubmed publisher..Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised...
- Zhang X, Langenick J, Traynor D, Babu M, Kay R, Patel K. Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the extreme resistance to cisplatin in Dictyostelium discoideum. PLoS Genet. 2009;5:e1000645 pubmed publisher..Other DNA damage-resistant organisms and chemoresistant cancer cells might adopt a similar strategy to develop resistance to DNA crosslinking agents. ..
- Donahue S, Lundberg R, Saplis R, Campbell C. Deficient regulation of DNA double-strand break repair in Fanconi anemia fibroblasts. J Biol Chem. 2003;278:29487-95 pubmed
- London T, Barber L, Mosedale G, Kelly G, Balasubramanian S, Hickson I, et al. FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. J Biol Chem. 2008;283:36132-9 pubmed publisher..Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication. ..
- Thomashevski A, High A, Drozd M, Shabanowitz J, Hunt D, Grant P, et al. The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments. J Biol Chem. 2004;279:26201-9 pubmed..These data will help define the biochemical role of the FA core complex in normal cell physiology as well as in the development of the FA disease state. ..
- Sims A, Spiteri E, Sims R, Arita A, Lach F, Landers T, et al. FANCI is a second monoubiquitinated member of the Fanconi anemia pathway. Nat Struct Mol Biol. 2007;14:564-7 pubmed..Biallelic mutations in the gene coding for this protein were found in cells from four FA patients, including an FA-I reference cell line. ..
- Zhi G, Wilson J, Chen X, Krause D, Xiao Y, Jones N, et al. Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is important for fanconi anemia pathway function and BRCA2 interaction. Cancer Res. 2009;69:8775-83 pubmed publisher..In vitro and in vivo experiments show that phosphorylation of S331 is mediated by CHK1, the S-phase checkpoint kinase implicated in the Fanconi anemia DNA repair pathway. ..
- Leung C, Gong Z, Chen J, Glover J. Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control. J Biol Chem. 2011;286:4292-301 pubmed publisher..Together with systematic mutagenesis studies, we highlight the role of key contacts in governing the unique specificity of the TopBP1-BACH1 interaction. ..
- Cantor S, Guillemette S. Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1. Future Oncol. 2011;7:253-61 pubmed publisher..In this article, we summarize the breast cancer-associated FANCJ mutations and discuss functional outcomes for DNA repair and tumor suppression. ..
- Whitney M, Royle G, Low M, Kelly M, Axthelm M, Reifsteck C, et al. Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene. Blood. 1996;88:49-58 pubmed..Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma. This previously unrecognized phenotype may form the basis for BM failure in human FA. ..
- Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D, et al. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Mol Cell. 2012;47:61-75 pubmed publisher..Thus, the RNF8-FAAP20 ubiquitin cascade is critical for recruiting FA core complex to ICLs and for normal function of the FA network. ..
- Grompe M, van de Vrugt H. The Fanconi family adds a fraternal twin. Dev Cell. 2007;12:661-2 pubmed..Like FANCD2, monoubiquitination of FANCI requires the FA core complex. Importantly, FANCI and FANCD2 monoubiquitination is co-dependent, suggesting a novel mechanism in ubiquitin conjugation. ..
- Xia B, Dorsman J, Ameziane N, de Vries Y, Rooimans M, Sheng Q, et al. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet. 2007;39:159-61 pubmed..PALB2-deficient cells showed hypersensitivity to cross-linking agents and lacked chromatin-bound BRCA2; these defects were corrected upon ectopic expression of PALB2 or by spontaneous reversion. ..