FANCD2

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Fanconi anemia, complementation group D2
Identifiers
Symbols FANCD2 ; FA-D2; FA4; FACD; FAD; FAD2; FANCD
External IDs OMIM613984 MGI2448480 HomoloGene13212 GeneCards: FANCD2 Gene
Orthologs
Species Human Mouse
Entrez 2177 211651
Ensembl ENSG00000144554 ENSMUSG00000034023
UniProt Q9BXW9 Q80V62
RefSeq (mRNA) NM_001018115 NM_001033244
RefSeq (protein) NP_001018125 NP_001028416
Location (UCSC) Chr 3:
10.03 – 10.1 Mb
Chr 6:
113.53 – 113.6 Mb
PubMed search [1] [2]

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene.[1][2][3][4] The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2 (this gene), FANCE, FANCF, FANCG, and FANCL.

Function[edit]

Fanconi anemia is a genetically homozygous recessive disorder characterized by chromosomal instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquitinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 and BRCA2) involved in homology-directed DNA repair. This monoubiquitination is required for interaction with the nuclease FAN1. Alternative splicing results in two transcript variants encoding different isoforms.[4]

Clinical significance[edit]

Tobacco smoke suppresses the expression of FANCD2, which codes for a DNA damage "caretaker" or repair mechanism.[3]

Interactions[edit]

FANCD2 has been shown to interact with:

References[edit]

  1. ^ Whitney M, Thayer M, Reifsteck C, Olson S, Smith L, Jakobs PM, Leach R, Naylor S, Joenje H, Grompe M (Nov 1995). "Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p". Nature Genetics 11 (3): 341–3. doi:10.1038/ng1195-341. PMID 7581463. 
  2. ^ Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M (Feb 2001). "Positional cloning of a novel Fanconi anemia gene, FANCD2". Molecular Cell 7 (2): 241–8. doi:10.1016/S1097-2765(01)00172-1. PMID 11239453. 
  3. ^ a b Hays LE, Zodrow DM, Yates JE, Deffebach ME, Jacoby DB, Olson SB, Pankow JF, Bagby GC (May 2008). "Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression". British Journal of Cancer 98 (10): 1653–61. doi:10.1038/sj.bjc.6604362. PMC 2391131. PMID 18475298. 
  4. ^ a b "Entrez Gene: FANCD2 Fanconi anemia, complementation group D2". 
  5. ^ Yuan F, El Hokayem J, Zhou W, Zhang Y (Sep 2009). "FANCI protein binds to DNA and interacts with FANCD2 to recognize branched structures". The Journal of Biological Chemistry 284 (36): 24443–52. doi:10.1074/jbc.m109.016006. PMID 19561358. 
  6. ^ Joo W, Xu G, Persky NS, Smogorzewska A, Rudge DG, Buzovetsky O, Elledge SJ, Pavletich NP (Jul 2011). "Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway". Science 333 (6040): 312–6. doi:10.1126/science.1205805. PMID 21764741. 
  7. ^ Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD (May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell 109 (4): 459–72. doi:10.1016/S0092-8674(02)00747-X. PMID 12086603. 
  8. ^ a b Reuter 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. PMID 14499622. 
  9. ^ a b Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (Jul 2003). "BRCA1-independent ubiquitination of FANCD2". Molecular Cell 12 (1): 247–54. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909. 
  10. ^ Wang X, Andreassen PR, D'Andrea AD (Jul 2004). "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin". Molecular and Cellular Biology 24 (13): 5850–62. doi:10.1128/MCB.24.13.5850-5862.2004. PMC 480901. PMID 15199141. 
  11. ^ a b Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG (Jun 2004). "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways". Human Molecular Genetics 13 (12): 1241–8. doi:10.1093/hmg/ddh135. PMID 15115758. 
  12. ^ a b Hejna J, Holtorf M, Hines J, Mathewson L, Hemphill A, Al-Dhalimy M, Olson SB, Moses RE (Apr 2008). "Tip60 is required for DNA interstrand cross-link repair in the Fanconi anemia pathway". The Journal of Biological Chemistry 283 (15): 9844–51. doi:10.1074/jbc.M709076200. PMC 2398728. PMID 18263878. 
  13. ^ 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. PMID 12649160. 
  14. ^ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (Jul 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal 21 (13): 3414–23. doi:10.1093/emboj/cdf355. PMC 125396. PMID 12093742. 
  15. ^ Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X (Jul 2003). "Menin associates with FANCD2, a protein involved in repair of DNA damage". Cancer Research 63 (14): 4204–10. PMID 12874027. 

Further reading[edit]

  • Hejna JA, Timmers CD, Reifsteck C, Bruun DA, Lucas LW, Jakobs PM, Toth-Fejel S, Unsworth N, Clemens SL, Garcia DK, Naylor SL, Thayer MJ, Olson SB, Grompe M, Moses RE (May 2000). "Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3". American Journal of Human Genetics 66 (5): 1540–1551. doi:10.1086/302896. PMC 1378015. PMID 10762542. 
  • Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD (Feb 2001). "Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway". Molecular Cell 7 (2): 249–262. doi:10.1016/S1097-2765(01)00173-3. PMID 11239454. 
  • Futaki M, Liu JM (Dec 2001). "Chromosomal breakage syndromes and the BRCA1 genome surveillance complex". Trends in Molecular Medicine 7 (12): 560–565. doi:10.1016/S1471-4914(01)02178-5. PMID 11733219. 
  • Wilson JB, Johnson MA, Stuckert AP, Trueman KL, May S, Bryant PE, Meyn RE, D'Andrea AD, Jones NJ (Dec 2001). "The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange". Carcinogenesis 22 (12): 1939–1946. doi:10.1093/carcin/22.12.1939. PMID 11751423. 
  • Grompe M (Jun 2002). "FANCD2: a branch-point in DNA damage response?". Nature Medicine 8 (6): 555–556. doi:10.1038/nm0602-555. PMID 12042798. 
  • Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD (May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell 109 (4): 459–472. doi:10.1016/S0092-8674(02)00747-X. PMID 12086603. 
  • Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (Jul 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal 21 (13): 3414–3423. doi:10.1093/emboj/cdf355. PMC 125396. PMID 12093742. 
  • Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD (Oct 2002). "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51". Blood 100 (7): 2414–20. doi:10.1182/blood-2002-01-0278. PMID 12239151. 
  • Tamary H, Bar-Yam R, Zemach M, Dgany O, Shalmon L, Yaniv I (Oct 2002). "The molecular biology of Fanconi anemia". The Israel Medical Association Journal 4 (10): 819–823. PMID 12389351. 
  • Nakanishi K, Taniguchi T, Ranganathan V, New HV, Moreau LA, Stotsky M, Mathew CG, Kastan MB, Weaver DT, D'Andrea AD (Dec 2002). "Interaction of FANCD2 and NBS1 in the DNA damage response". Nature Cell Biology 4 (12): 913–920. doi:10.1038/ncb879. PMID 12447395. 
  • Goldberg M, Stucki M, Falck J, D'Amours D, Rahman D, Pappin D, Bartek J, Jackson SP (Feb 2003). "MDC1 is required for the intra-S-phase DNA damage checkpoint". Nature 421 (6926): 952–6. doi:10.1038/nature01445. PMID 12607003. 
  • Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature 421 (6926): 961–6. doi:10.1038/nature01446. PMID 12607005. 
  • Gordon SM, Buchwald M (Jul 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood 102 (1): 136–141. doi:10.1182/blood-2002-11-3517. PMID 12649160. 
  • Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X (Jul 2003). "Menin associates with FANCD2, a protein involved in repair of DNA damage". Cancer Research 63 (14): 4204–10. PMID 12874027. 
  • Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (Jul 2003). "BRCA1-independent ubiquitination of FANCD2". Molecular Cell 12 (1): 247–254. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909. 
  • 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): 165–170. doi:10.1038/ng1241. PMID 12973351. 
  • Reuter 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): 211–221. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622. 
  • Wang X, Kennedy RD, Ray K, Stuckert P, Ellenberger T, D'Andrea AD (Apr 2007). "Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway". Molecular and Cellular Biology 27 (8): 3098–108. doi:10.1128/MCB.02357-06. PMC 1899922. PMID 17296736.