Fanconi anemia, complementation group C explained
Fanconi anemia group C protein is a protein that in humans is encoded by the FANCC gene.[1] [2] This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.[3]
Structure
Align: | left |
Symbol: | Fanconi_C |
Fanconi anaemia group C protein |
Pfam: | PF02106 |
Interpro: | IPR000686 |
Function
A nuclear complex containing FANCC protein (as well as FANCA, FANCF and FANCG) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform.[4] In normal, non-mutant, cells FANCD2 is mono-ubiquinated in response to DNA damage. FANCC together with FANCE acts as the substrate adaptor for this reaction [5] Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes. Activated FANCD2 protein may function prior to the initiation of meiotic recombination, perhaps to prepare chromosomes for synapsis, or to regulate subsequent recombination events.
FANCC(-/-) mutant male and female mice have compromised gametogenesis, leading to markedly impaired fertility, a characteristic of Fanconi anemia patients.[6] Both male and female FANCC mutant mice have reduced numbers of germ cells.[7]
Interactions
Fanconi anemia, complementation group C has been shown to interact with:
Further reading
- Strathdee CA, Gavish H, Shannon WR, Buchwald M . Cloning of cDNAs for Fanconi's anaemia by functional complementation . Nature . 356 . 6372 . 763–7 . Apr 1992 . 1574115 . 10.1038/356763a0 . 1992Natur.356..763S . 4250632 .
- Strathdee CA, Gavish H, Shannon WR, Buchwald M . Cloning of cDNAs for Fanconi's anaemia by functional complementation . Nature . 358 . 6385 . 434 . Jul 1992 . 1641028 . 10.1038/358434a0 . 1992Natur.358..434S . free .
- Verlander PC, Kaporis A, Liu Q, Zhang Q, Seligsohn U, Auerbach AD . Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population . Blood . 86 . 11 . 4034–8 . December 1995 . 7492758 . 10.1182/blood.V86.11.4034.bloodjournal86114034. free .
- Yamashita T, Barber DL, Zhu Y, Wu N, D'Andrea AD . The Fanconi anemia polypeptide FACC is localized to the cytoplasm . Proceedings of the National Academy of Sciences of the United States of America . 91 . 14 . 6712–6 . Jul 1994 . 7517562 . 44273 . 10.1073/pnas.91.14.6712 . 1994PNAS...91.6712Y . free .
- Segal GM, Magenis RE, Brown M, Keeble W, Smith TD, Heinrich MC, Bagby GC . Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells . The Journal of Clinical Investigation . 94 . 2 . 846–52 . Aug 1994 . 7518843 . 296166 . 10.1172/JCI117405 .
- Youssoufian H . Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells . Proceedings of the National Academy of Sciences of the United States of America . 91 . 17 . 7975–9 . Aug 1994 . 8058745 . 44527 . 10.1073/pnas.91.17.7975 . 1994PNAS...91.7975Y . free .
- Whitney MA, Jakobs P, Kaback M, Moses RE, Grompe M . The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population . Human Mutation . 3 . 4 . 339–41 . 1994 . 8081385 . 10.1002/humu.1380030402 . 22001726 . free .
- Murer-Orlando M, Llerena JC, Birjandi F, Gibson RA, Mathew CG . FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia . Lancet . 342 . 8872 . 686 . Sep 1993 . 8103176 . 10.1016/0140-6736(93)91800-2 . 7355624 .
- Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
- Verlander PC, Lin JD, Udono MU, Zhang Q, Gibson RA, Mathew CG, Auerbach AD . Mutation analysis of the Fanconi anemia gene FACC . American Journal of Human Genetics . 54 . 4 . 595–601 . Apr 1994 . 8128956 . 1918103 .
- Whitney MA, Saito H, Jakobs PM, Gibson RA, Moses RE, Grompe M . A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews . Nature Genetics . 4 . 2 . 202–5 . Jun 1993 . 8348157 . 10.1038/ng0693-202 . 12160503 .
- Gibson RA, Buchwald M, Roberts RG, Mathew CG . Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR . Human Molecular Genetics . 2 . 1 . 35–8 . Jan 1993 . 8490620 . 10.1093/hmg/2.1.35 .
- Gavish H, dos Santos CC, Buchwald M . A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein . Human Molecular Genetics . 2 . 2 . 123–6 . Feb 1993 . 8499901 . 10.1093/hmg/2.2.123 .
- Youssoufian H, Li Y, Martin ME, Buchwald M . Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele . The Journal of Clinical Investigation . 97 . 4 . 957–62 . Feb 1996 . 8613549 . 507141 . 10.1172/JCI118519 .
- Yamashita T, Wu N, Kupfer G, Corless C, Joenje H, Grompe M, D'Andrea AD . Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity . Blood . 87 . 10 . 4424–32 . May 1996 . 8639804 . 10.1182/blood.V87.10.4424.bloodjournal87104424. free .
- Lo Ten Foe JR, Rooimans MA, Joenje H, Arwert F . Novel frameshift mutation (1806insA) in exon 14 of the Fanconi anemia C gene, FAC . Human Mutation . 7 . 3 . 264–5 . 1996 . 8829660 . 10.1002/(SICI)1098-1004(1996)7:3<264::AID-HUMU11>3.0.CO;2-0 . 27932876 . free .
- Gibson RA, Morgan NV, Goldstein LH, Pearson IC, Kesterton IP, Foot NJ, Jansen S, Havenga C, Pearson T, de Ravel TJ, Cohn RJ, Marques IM, Dokal I, Roberts I, Marsh J, Ball S, Milner RD, Llerena JC, Samochatova E, Mohan SP, Vasudevan P, Birjandi F, Hajianpour A, Murer-Orlando M, Mathew CG . Novel mutations and polymorphisms in the Fanconi anemia group C gene . Human Mutation . 8 . 2 . 140–8 . 1996 . 8844212 . 10.1002/(SICI)1098-1004(1996)8:2<140::AID-HUMU6>3.0.CO;2-F . 11474873 . free .
- Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S, D'Andrea AD . The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2 . Blood . 90 . 3 . 1047–54 . Aug 1997 . 9242535 . 10.1182/blood.V90.3.1047. free .
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
External links
Notes and References
- Strathdee CA, Duncan AM, Buchwald M . Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9 . Nature Genetics . 1 . 3 . 196–8 . Jun 1992 . 1303234 . 10.1038/ng0692-196 . 7341515 .
- Web site: Entrez Gene: FANCC Fanconi anemia, complementation group C.
- PMC . Europe . Europe PMC . Cell Communication and Signaling . 2017 . 15 . 1 . 41 . 10.1186/s12964-017-0195-9 . 29017571 . 5635482 . en . free .
- Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD . Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway . Mol. Cell . 7 . 2 . 249–62 . 2001 . 11239454 . 10.1016/s1097-2765(01)00173-3. free .
- van Twest . S . Murphy . VJ . Hodson . C . Tan . W . Swuec . P . O'Rourke . JJ . Heierhorst . J . Crismani . W . Deans . AJ . Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway. . Molecular Cell . 19 January 2017 . 65 . 2 . 247–259 . 10.1016/j.molcel.2016.11.005 . 27986371. free . 2434/618936 . free .
- Chen M, Tomkins DJ, Auerbach W, McKerlie C, Youssoufian H, Liu L, Gan O, Carreau M, Auerbach A, Groves T, Guidos CJ, Freedman MH, Cross J, Percy DH, Dick JE, Joyner AL, Buchwald M . Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia . Nat. Genet. . 12 . 4 . 448–51 . 1996 . 8630504 . 10.1038/ng0496-448 . 34666783 .
- Whitney MA, Royle G, Low MJ, Kelly MA, Axthelm MK, Reifsteck C, Olson S, Braun RE, Heinrich MC, Rathbun RK, Bagby GC, Grompe M . Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene . Blood . 88 . 1 . 49–58 . 1996 . 8704201 . 10.1182/blood.V88.1.49.49. free . 1773/4433 . free .
- Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S, D'Andrea AD . The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2 . Blood . 90 . 3 . 1047–54 . Aug 1997 . 9242535 . 10.1182/blood.V90.3.1047. free .
- Garcia-Higuera I, Kuang Y, Näf D, Wasik J, D'Andrea AD . Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex . Molecular and Cellular Biology . 19 . 7 . 4866–73 . Jul 1999 . 10373536 . 84285 . 10.1128/mcb.19.7.4866.
- Reuter T, Herterich S, Bernhard O, Hoehn H, Gross HJ . Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system . Blood . 95 . 2 . 719–20 . Jan 2000 . 10627486 . 10.1182/blood.V95.2.719.
- Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM . The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments . The Journal of Biological Chemistry . 279 . 25 . 26201–9 . Jun 2004 . 15082718 . 10.1074/jbc.M400091200 . free .
- Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W . A novel ubiquitin ligase is deficient in Fanconi anemia . Nature Genetics . 35 . 2 . 165–70 . Oct 2003 . 12973351 . 10.1038/ng1241 . 10149290 .
- Taniguchi T, D'Andrea AD . The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC . Blood . 100 . 7 . 2457–62 . October 2002 . 12239156 . 10.1182/blood-2002-03-0860 . free .
- Otsuki T, Young DB, Sasaki DT, Pando MP, Li J, Manning A, Hoekstra M, Hoatlin ME, Mercurio F, Liu JM . Fanconi anemia protein complex is a novel target of the IKK signalsome . Journal of Cellular Biochemistry . 86 . 4 . 613–23 . 12210728 . 10.1002/jcb.10270 . 2002 . 42471384 . Submitted manuscript .
- Gordon SM, Buchwald M . Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems . Blood . 102 . 1 . 136–41 . Jul 2003 . 12649160 . 10.1182/blood-2002-11-3517 .
- Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG . Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway . Human Molecular Genetics . 10 . 4 . 423–9 . Feb 2001 . 11157805 . 10.1093/hmg/10.4.423. free .
- Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ . FANCE: the link between Fanconi anaemia complex assembly and activity . The EMBO Journal . 21 . 13 . 3414–23 . Jul 2002 . 12093742 . 125396 . 10.1093/emboj/cdf355 .
- de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H . The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG . Human Molecular Genetics . 9 . 18 . 2665–74 . Nov 2000 . 11063725 . 10.1093/hmg/9.18.2665. free .
- Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP . The Fanconi anemia gene product FANCF is a flexible adaptor protein . The Journal of Biological Chemistry . 279 . 38 . 39421–30 . Sep 2004 . 15262960 . 10.1074/jbc.M407034200 . free .
- Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, Buchwald M . Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1 . Nature Medicine . 7 . 7 . 814–20 . Jul 2001 . 11433346 . 10.1038/89937 . 35177844 .
- Pang Q, Christianson TA, Keeble W, Koretsky T, Bagby GC . The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC . The Journal of Biological Chemistry . 277 . 51 . 49638–43 . December 2002 . 12397061 . 10.1074/jbc.M209386200 . free .
- McMahon LW, Walsh CE, Lambert MW . Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex . The Journal of Biological Chemistry . 274 . 46 . 32904–8 . Nov 1999 . 10551855 . 10.1074/jbc.274.46.32904. free .
- McMahon LW, Sangerman J, Goodman SR, Kumaresan K, Lambert MW . Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links . Biochemistry . 40 . 24 . 7025–34 . Jun 2001 . 11401546 . 10.1021/bi002917g.
- Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA . Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport . Experimental Cell Research . 289 . 2 . 211–21 . Oct 2003 . 14499622 . 10.1016/s0014-4827(03)00261-1.
- Pang Q, Fagerlie S, Christianson TA, Keeble W, Faulkner G, Diaz J, Rathbun RK, Bagby GC . The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors . Molecular and Cellular Biology . 20 . 13 . 4724–35 . Jul 2000 . 10848598 . 85895 . 10.1128/mcb.20.13.4724-4735.2000.
- Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C, Olson S, Bagby GC . The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality . Blood . 98 . 5 . 1392–401 . Sep 2001 . 11520787 . 10.1182/blood.v98.5.1392. 12153966 . free .
- Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD . A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF . Blood . 94 . 11 . 3737–47 . December 1999 . 10572087 . 10.1182/blood.V94.11.3737.