The protein encoded by this gene delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia.[2]
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.[3] 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 [4] 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.[3]
FANCC(-/-) mutant male and female mice have compromised gametogenesis, leading to markedly impaired fertility, a characteristic of Fanconi anemia patients.[5] Both male and female FANCC mutant mice have reduced numbers of germ cells.[6]
Interactions
Fanconi anemia, complementation group C has been shown to interact with:
↑Strathdee CA, Duncan AM, Buchwald M (Jun 1992). "Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9". Nature Genetics. 1 (3): 196–8. doi:10.1038/ng0692-196. PMID1303234.
↑ 3.03.1Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD (2001). "Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway". Mol. Cell. 7 (2): 249–62. doi:10.1016/s1097-2765(01)00173-3. PMID11239454.
↑van Twest, S; Murphy, VJ; Hodson, C; Tan, W; Swuec, P; O'Rourke, JJ; Heierhorst, J; Crismani, W; Deans, AJ (19 January 2017). "Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway". Molecular Cell. 65 (2): 247–259. doi:10.1016/j.molcel.2016.11.005. PMID27986371.
↑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 (1996). "Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia". Nat. Genet. 12 (4): 448–51. doi:10.1038/ng0496-448. PMID8630504.
↑Whitney MA, Royle G, Low MJ, Kelly MA, Axthelm MK, Reifsteck C, Olson S, Braun RE, Heinrich MC, Rathbun RK, Bagby GC, Grompe M (1996). "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. PMID8704201.
↑ 7.07.17.27.37.4Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (Oct 2003). "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. doi:10.1016/s0014-4827(03)00261-1. PMID14499622.
↑Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S, D'Andrea AD (Aug 1997). "The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2". Blood. 90 (3): 1047–54. PMID9242535.
↑ 9.09.1McMahon LW, Walsh CE, Lambert MW (Nov 1999). "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. doi:10.1074/jbc.274.46.32904. PMID10551855.
↑ 10.010.1de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H (Nov 2000). "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG". Human Molecular Genetics. 9 (18): 2665–74. doi:10.1093/hmg/9.18.2665. PMID11063725.
↑Reuter T, Herterich S, Bernhard O, Hoehn H, Gross HJ (Jan 2000). "Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system". Blood. 95 (2): 719–20. PMID10627486.
↑Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM (Jun 2004). "The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments". The Journal of Biological Chemistry. 279 (25): 26201–9. doi:10.1074/jbc.M400091200. PMID15082718.
↑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 (Oct 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–70. doi:10.1038/ng1241. PMID12973351.
↑ 15.015.1Taniguchi T, D'Andrea AD (Oct 2002). "The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC". Blood. 100 (7): 2457–62. doi:10.1182/blood-2002-03-0860. PMID12239156.
↑ 17.017.1Léveillé 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 (Sep 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein". The Journal of Biological Chemistry. 279 (38): 39421–30. doi:10.1074/jbc.M407034200. PMID15262960.
↑Gordon SM, Buchwald M (Jul 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood. 102 (1): 136–41. doi:10.1182/blood-2002-11-3517. PMID12649160.
↑Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (Feb 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Human Molecular Genetics. 10 (4): 423–9. doi:10.1093/hmg/10.4.423. PMID11157805.
↑Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, Buchwald M (Jul 2001). "Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1". Nature Medicine. 7 (7): 814–20. doi:10.1038/89937. PMID11433346.
↑Pang Q, Christianson TA, Keeble W, Koretsky T, Bagby GC (Dec 2002). "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. doi:10.1074/jbc.M209386200. PMID12397061.
↑McMahon LW, Sangerman J, Goodman SR, Kumaresan K, Lambert MW (Jun 2001). "Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links". Biochemistry. 40 (24): 7025–34. doi:10.1021/bi002917g. PMID11401546.
↑Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C, Olson S, Bagby GC (Sep 2001). "The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality". Blood. 98 (5): 1392–401. doi:10.1182/blood.v98.5.1392. PMID11520787.
↑Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (Dec 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. PMID10572087.
Further reading
Strathdee CA, Gavish H, Shannon WR, Buchwald M (Apr 1992). "Cloning of cDNAs for Fanconi's anaemia by functional complementation". Nature. 356 (6372): 763–7. doi:10.1038/356763a0. PMID1574115.
Strathdee CA, Gavish H, Shannon WR, Buchwald M (Jul 1992). "Cloning of cDNAs for Fanconi's anaemia by functional complementation". Nature. 358 (6385): 434. doi:10.1038/358434a0. PMID1641028.
Verlander PC, Kaporis A, Liu Q, Zhang Q, Seligsohn U, Auerbach AD (Dec 1995). "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. PMID7492758. Check date values in: |year= / |date= mismatch (help)
Whitney MA, Jakobs P, Kaback M, Moses RE, Grompe M (1994). "The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population". Human Mutation. 3 (4): 339–41. doi:10.1002/humu.1380030402. PMID8081385.
Murer-Orlando M, Llerena JC, Birjandi F, Gibson RA, Mathew CG (Sep 1993). "FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia". Lancet. 342 (8872): 686. doi:10.1016/0140-6736(93)91800-2. PMID8103176.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Whitney MA, Saito H, Jakobs PM, Gibson RA, Moses RE, Grompe M (Jun 1993). "A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews". Nature Genetics. 4 (2): 202–5. doi:10.1038/ng0693-202. PMID8348157.
Gibson RA, Buchwald M, Roberts RG, Mathew CG (Jan 1993). "Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR". Human Molecular Genetics. 2 (1): 35–8. doi:10.1093/hmg/2.1.35. PMID8490620.
Gavish H, dos Santos CC, Buchwald M (Feb 1993). "A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein". Human Molecular Genetics. 2 (2): 123–6. doi:10.1093/hmg/2.2.123. PMID8499901.
Yamashita T, Wu N, Kupfer G, Corless C, Joenje H, Grompe M, D'Andrea AD (May 1996). "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. PMID8639804.
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 (1996). "Novel mutations and polymorphisms in the Fanconi anemia group C gene". Human Mutation. 8 (2): 140–8. doi:10.1002/(SICI)1098-1004(1996)8:2<140::AID-HUMU6>3.0.CO;2-F. PMID8844212.
Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S, D'Andrea AD (Aug 1997). "The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2". Blood. 90 (3): 1047–54. PMID9242535.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.