Gene Symbol: Fancd2
Description: Fanconi anemia, complementation group D2
Alias: 2410150O07Rik, AU015151, BB137857, FA-D2, FA4, FACD, FAD, FANCD, Fanconi anemia group D2 protein homolog
Species: mouse
Products:     Fancd2

Top Publications

  1. Park J, Pitot H, Strati K, Spardy N, Duensing S, Grompe M, et al. Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res. 2010;70:9959-68 pubmed publisher
    ..importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2(-/-)) to establish K14E7/FancD2(-/-) and K14E7/FancD2(+/+) mice and monitored their ..
  2. Houghtaling S, Granville L, Akkari Y, Torimaru Y, Olson S, Finegold M, et al. Heterozygosity for p53 (Trp53+/-) accelerates epithelial tumor formation in fanconi anemia complementation group D2 (Fancd2) knockout mice. Cancer Res. 2005;65:85-91 pubmed
    ..We have previously reported an increased incidence of epithelial tumors in Fancd2 knockout mice...
  3. 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
    ..Recent studies suggest that the FA pathway may also play a role in mitosis, since FANCD2 and FANCI, the 2 key FA proteins, are localized to the extremities of ultrafine DNA bridges (UFBs), which link ..
  4. Parmar K, Kim J, Sykes S, Shimamura A, Stuckert P, Zhu K, et al. Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem Cells. 2010;28:1186-95 pubmed publisher
    ..Central events in the FA pathway are the monoubiquitination of the Fancd2 protein and the removal of ubiquitin by the deubiquitinating enzyme, Usp1...
  5. Wong J, Alon N, McKerlie C, Huang J, Meyn M, Buchwald M. Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia. Hum Mol Genet. 2003;12:2063-76 pubmed
    ..However, the localization of Rad51, Brca1, Fancd2 and Mlh1 appeared normal on Fanca(tm1Hsc) homozygous meiotic chromosomes...
  6. Bunting S, Callén E, Kozak M, Kim J, Wong N, López Contreras A, et al. BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair. Mol Cell. 2012;46:125-35 pubmed publisher Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi anemia pathway for ICL repair...
  7. Houghtaling S, Timmers C, Noll M, Finegold M, Jones S, Meyn M, et al. Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes Dev. 2003;17:2021-35 pubmed
    ..investigate the in vivo function of the FA pathway, mice with a targeted deletion in the distally acting FA gene Fancd2 were created...
  8. van de Vrugt H, Eaton L, Hanlon Newell A, Al Dhalimy M, Liskay R, Olson S, et al. Embryonic lethality after combined inactivation of Fancd2 and Mlh1 in mice. Cancer Res. 2009;69:9431-8 pubmed publisher
    ..To determine the consequences of combined Fanconi anemia (FA) and mismatch repair pathway inactivation, defects in Fancd2 and Mlh1 were combined in one mouse model...
  9. García Rubio M, Pérez Calero C, Barroso S, Tumini E, Herrera Moyano E, Rosado I, et al. The Fanconi Anemia Pathway Protects Genome Integrity from R-loops. PLoS Genet. 2015;11:e1005674 pubmed publisher
    ..Using human and murine cells defective in FANCD2 or FANCA and primary bone marrow cells from FANCD2 deficient mice, we show that the FA pathway removes R loops, ..

More Information


  1. Ceccaldi R, Liu J, Amunugama R, Hajdu I, Primack B, Petalcorin M, et al. Homologous-recombination-deficient tumours are dependent on Pol?-mediated repair. Nature. 2015;518:258-62 pubmed publisher
    ..Consistent with these results, genetic inactivation of an HR gene (Fancd2) and Polq in mice results in embryonic lethality...
  2. Li X, Li L, Li J, Sipple J, Schick J, Mehta P, et al. Concomitant inactivation of foxo3a and fancc or fancd2 reveals a two-tier protection from oxidative stress-induced hydrocephalus. Antioxid Redox Signal. 2014;21:1675-92 pubmed publisher
    ..More than 50% of Foxo3a(-/-) Fancc(-/-) or Foxo3a(-/-) Fancd2(-/-) mice die during embryonic development or within 6 months of life as a result of hydrocephalus characterized ..
  3. Wang J, Sarkar T, Zhou M, Sharan S, Ritt D, Veenstra T, et al. CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD)-mediated nuclear import of FANCD2 by IPO4 augments cellular response to DNA damage. Proc Natl Acad Sci U S A. 2010;107:16131-6 pubmed publisher
    ..we found that C/EBPδ promotes monoubiquitination of the Fanconi anemia complementation group D2 protein (FANCD2), which is necessary for its function in replication-associated DNA repair...
  4. Ho G, Margossian S, Taniguchi T, D Andrea A. Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance. Mol Cell Biol. 2006;26:7005-15 pubmed
    ..Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event...
  5. Matsuzaki K, Borel V, Adelman C, Schindler D, Boulton S. FANCJ suppresses microsatellite instability and lymphomagenesis independent of the Fanconi anemia pathway. Genes Dev. 2015;29:2532-46 pubmed publisher
    ..In contrast, MSI is not observed in Fancd2(-/-) mice but is prevalent in human FA-J patients...
  6. Jamsai D, O Connor A, Deboer K, Clark B, Smith S, Browne C, et al. Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse. PLoS ONE. 2013;8:e56955 pubmed publisher
    ..In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36...
  7. Pradhan A, Ustiyan V, Zhang Y, Kalin T, Kalinichenko V. Forkhead transcription factor FoxF1 interacts with Fanconi anemia protein complexes to promote DNA damage response. Oncotarget. 2016;7:1912-26 pubmed publisher
    ..FoxF1 co-localizes with FANCD2 in DNA repair foci in cultured cells and tumor tissues obtained from cisplatin-treated mice...
  8. Rulten S, Hodder E, Ripley T, Stephens D, Mayne L. Alcohol induces DNA damage and the Fanconi anemia D2 protein implicating FANCD2 in the DNA damage response pathways in brain. Alcohol Clin Exp Res. 2008;32:1186-96 pubmed publisher
    ..of ethanol to generate DNA strand breaks, predicted substrates for the Fanc pathway and the potential role of FANCD2 in the DDR to ethanol in brain...
  9. Hays L, Zodrow D, Yates J, Deffebach M, Jacoby D, Olson S, et al. Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. Br J Cancer. 2008;98:1653-61 pubmed publisher
    ..Here, we show that cigarette smoke condensate (CSC) inhibited translation of FANCD2 mRNA (but not FANCC or FANCG) in normal airway epithelial cells and that this suppression of FANCD2 expression was ..
  10. Kim J, Parmar K, Huang M, Weinstock D, Ruit C, Kutok J, et al. Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell. 2009;16:314-20 pubmed publisher
    ..A critical step in this pathway is the monoubiquitination and deubiquitination of FANCD2. Deubiquitination of FANCD2 is mediated by the ubiquitin protease, USP1...
  11. Chen H, Juan H, Wong Y, Tsai J, Fann M. Cdk12 Regulates Neurogenesis and Late-Arising Neuronal Migration in the Developing Cerebral Cortex. Cereb Cortex. 2017;27:2289-2302 pubmed publisher
    ..Thus, Cdk12 is crucial to the repair of DNA damage during the proliferation of NPCs and is also central to the proper migration of late-arising neurons. ..
  12. Adelman C, Lolo R, Birkbak N, Murina O, Matsuzaki K, Horejsi Z, et al. HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis. Nature. 2013;502:381-4 pubmed publisher
    ..Thus, our results reveal a critical role for HELQ in replication-coupled DNA repair, germ cell maintenance and tumour suppression in mammals. ..
  13. Pontel L, Rosado I, Burgos Barragan G, Garaycoechea J, Yu R, Arends M, et al. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen. Mol Cell. 2015;60:177-88 pubmed publisher
    ..The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein...
  14. Yoon Y, Storm K, Kamimae Lanning A, Goloviznina N, Kurre P. Endogenous DNA Damage Leads to p53-Independent Deficits in Replicative Fitness in Fetal Murine Fancd2-/- Hematopoietic Stem and Progenitor Cells. Stem Cell Reports. 2016;7:840-853 pubmed publisher
    ..Here, we reveal a fetal HSPC pool in Fancd2-/- mice with compromised clonogenicity and repopulation...
  15. Song X, Xie Y, Kang R, Hou W, Sun X, Epperly M, et al. FANCD2 protects against bone marrow injury from ferroptosis. Biochem Biophys Res Commun. 2016;480:443-449 pubmed publisher
    ..Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow ..
  16. Park E, Kim J, Primack B, Weinstock D, Moreau L, Parmar K, et al. Inactivation of Uaf1 causes defective homologous recombination and early embryonic lethality in mice. Mol Cell Biol. 2013;33:4360-70 pubmed publisher
    ..Absence of this complex leads to increased cellular levels of ubiquitinated FANCD2 (FANCD2-Ub) and ubiquitinated PCNA (PCNA-Ub)...
  17. Freie B, Ciccone S, Li X, Plett P, Orschell C, Srour E, et al. A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint. J Biol Chem. 2004;279:50986-93 pubmed
    ..Finally, fibroblasts lacking FANCD2 were found to have a G2 checkpoint phenotype similar to FANCC-deficient cells, indicating that FANCD2, which is ..
  18. Wang X, Andreassen P, D Andrea A. Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol. 2004;24:5850-62 pubmed
    ..Here we show that monoubiquitination of FANCD2, which is activated by DNA damage, is required for targeting of FANCD2 to chromatin, where it interacts with BRCA2...
  19. Atanassov B, Barrett J, Davis B. Homozygous germ line mutation in exon 27 of murine Brca2 disrupts the Fancd2-Brca2 pathway in the homologous recombination-mediated DNA interstrand cross-links' repair but does not affect meiosis. Genes Chromosomes Cancer. 2005;44:429-37 pubmed
    ..Immunoprecipitation experiments showed that Fancd2 did not coprecipitate with the mutated Brca2...
  20. Zhang H, Kozono D, O Connor K, Vidal Cardenas S, Rousseau A, Hamilton A, et al. TGF-β Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia. Cell Stem Cell. 2016;18:668-81 pubmed publisher
    ..Together, our results suggest that elevated TGF-β signaling contributes to BMF in FA by impairing HSPC function and may be a potential therapeutic target for the treatment of FA. ..
  21. Park J, Shin M, Pitot H, Lambert P. High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins. PLoS ONE. 2013;8:e75056 pubmed publisher
    ..HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor...
  22. Thongthip S, Bellani M, Gregg S, Sridhar S, Conti B, Chen Y, et al. Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction. Genes Dev. 2016;30:645-59 pubmed publisher
    Deficiency of FANCD2/FANCI-associated nuclease 1 (FAN1) in humans leads to karyomegalic interstitial nephritis (KIN), a rare hereditary kidney disease characterized by chronic renal fibrosis, tubular degeneration, and characteristic ..
  23. Zhang X, Hou W, Epperly M, Rigatti L, Wang H, Franicola D, et al. Evolution of malignant plasmacytoma cell lines from K14E7 Fancd2-/- mouse long-term bone marrow cultures. Oncotarget. 2016;7:68449-68472 pubmed publisher
    ..Virus (HPV E7) oncogene on hematopoiesis in long-term bone marrow cultures (LTBMCs) derived from K14E7 (FVB) Fancd2-/- (129/Sv), K14E7 Fancd2+/+, Fancd2-/-, and control (FVB X 129/Sv) Fl mice...
  24. Park E, Kim H, Kim J, Primack B, Vidal Cardenas S, Xu Y, et al. FANCD2 activates transcription of TAp63 and suppresses tumorigenesis. Mol Cell. 2013;50:908-18 pubmed publisher
    ..A critical step is the monoubiquitination of the FANCD2 protein, and cells from most FA patients are deficient in this step...
  25. Langevin F, Crossan G, Rosado I, Arends M, Patel K. Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice. Nature. 2011;475:53-8 pubmed publisher
    ..Our results show that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development of Fancd2(-/-) embryos...
  26. Peng M, Xie J, Ucher A, Stavnezer J, Cantor S. Crosstalk between BRCA-Fanconi anemia and mismatch repair pathways prevents MSH2-dependent aberrant DNA damage responses. EMBO J. 2014;33:1698-712 pubmed publisher
    Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown...
  27. Wang D, Chen Y, Ruan M, Zhou A, Qian Y, Chen C. Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress. Neurosci Lett. 2016;635:24-32 pubmed publisher
    ..activated the Fanconi anemia (FA) pathway, which was characterized by increases in monoubiquitination of Fanci and Fancd2 and enhancement of the interaction between above two proteins...
  28. Garaycoechea J, Crossan G, Langevin F, Daly M, Arends M, Patel K. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function. Nature. 2012;489:571-5 pubmed publisher
    ..combined inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathway (Fancd2 knockout) display developmental defects, a predisposition to leukaemia, and are susceptible to the toxic effects ..
  29. Zhang Q, Tang W, Deater M, Phan N, Marcogliese A, Li H, et al. Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice. Blood. 2016;128:2774-2784 pubmed
    ..Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2-/- mice. Metformin is the first compound reported to improve both of these FA phenotypes...
  30. Alavattam K, Kato Y, Sin H, Maezawa S, Kowalski I, Zhang F, et al. Elucidation of the Fanconi Anemia Protein Network in Meiosis and Its Function in the Regulation of Histone Modifications. Cell Rep. 2016;17:1141-1157 pubmed publisher
    ..We reveal a network of FA and DDR proteins in which FA core factors FANCA, FANCB, and FANCC are essential for FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) ..
  31. Skinner A, O Neill S, Grompe M, Kurre P. CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Exp Hematol. 2008;36:273-82 pubmed publisher
  32. Bogliolo M, Lyakhovich A, Callen E, Castella M, Cappelli E, Ramirez M, et al. Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability. EMBO J. 2007;26:1340-51 pubmed
    ..The central FA protein FANCD2 is known to relocate to chromatin upon DNA damage in a poorly understood process...
  33. Juan H, Lin Y, Chen H, Fann M. Cdk12 is essential for embryonic development and the maintenance of genomic stability. Cell Death Differ. 2016;23:1038-48 pubmed publisher
    ..Furthermore, the expression levels of various DNA damage response genes, namely Atr, Brca1, Fanci and Fancd2, are reduced in Cdk12(-/-) embryos...
  34. Du W, Erden O, Wilson A, Sipple J, Schick J, Mehta P, et al. Deletion of Fanca or Fancd2 dysregulates Treg in mice. Blood. 2014;123:1938-47 pubmed publisher
    ..However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-..
  35. Zhang Q, Marquez Loza L, Eaton L, Duncan A, Goldman D, Anur P, et al. Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. Blood. 2010;116:5140-8 pubmed publisher
    ..In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2(-/-) mice have readily measurable hematopoietic defects...
  36. Jiang Q, Paramasivam M, Aressy B, Wu J, Bellani M, Tong W, et al. MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links. Genes Dev. 2015;29:1955-68 pubmed publisher
    ..MERIT40 was rapidly recruited to ICL lesions prior to FANCD2, and Merit40-null cells exhibited delayed ICL unhooking coupled with reduced end resection and homologous ..
  37. Amarachintha S, Sertorio M, Wilson A, Li X, Pang Q. Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling. Stem Cells. 2015;33:3382-96 pubmed publisher
    ..cobblestone area-forming cell assay revealed that TOFA significantly increased cobblestone colonies in Fanca-/- or Fancd2-/- cocultures compared to untreated cocultures...
  38. Houghtaling S, Newell A, Akkari Y, Taniguchi T, Olson S, Grompe M. Fancd2 functions in a double strand break repair pathway that is distinct from non-homologous end joining. Hum Mol Genet. 2005;14:3027-33 pubmed
    ..Many of the proteins form a nuclear complex necessary for the mono-ubiquitination of the downstream protein, Fancd2. To further investigate the role of the FA pathway in repair of DSBs, we generated Fancd2(-/-)/Prkdc(sc/sc) double ..
  39. Zhang Q, Eaton L, Snyder E, Houghtaling S, Mitchell J, Finegold M, et al. Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. Cancer Res. 2008;68:1601-8 pubmed publisher
    ..FA patients have an elevated risk of developing hematologic malignancies and solid tumors. Using Fancd2(-/-) knockout mice as a model of FA, we examined the potential of tempol, a nitroxide antioxidant and a superoxide ..
  40. Suzuki S, Racine R, Manalo N, Cantor S, Raffel G. Impairment of fetal hematopoietic stem cell function in the absence of Fancd2. Exp Hematol. 2017;48:79-86 pubmed publisher
    ..To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of embryonic day 14.5 (E14...
  41. Reliene R, Yamamoto M, Rao P, Schiestl R. Genomic instability in mice is greater in Fanconi anemia caused by deficiency of Fancd2 than Fancg. Cancer Res. 2010;70:9703-10 pubmed publisher
    ..FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI...
  42. Joo W, Xu G, Persky N, Smogorzewska A, Rudge D, Buzovetsky O, et al. Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science. 2011;333:312-6 pubmed publisher
    ..Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3...
  43. Lachaud C, Moreno A, Marchesi F, Toth R, Blow J, Rouse J. Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability. Science. 2016;351:846-9 pubmed publisher
    Mono-ubiquitination of Fancd2 is essential for repairing DNA interstrand cross-links (ICLs), but the underlying mechanisms are unclear. The Fan1 nuclease, also required for ICL repair, is recruited to ICLs by ubiquitinated (Ub) Fancd2...
  44. Pitman J, McNeilly A, McNeilly J, Hays L, Bagby G, Sawyer H, et al. The fate of granulosa cells following premature oocyte loss and the development of ovarian cancers. Int J Dev Biol. 2012;56:949-58 pubmed publisher
    ..Dazl-KO and FancD2-KO mice and BMP15-KO sheep are animal models in which germ cells or oocytes are lost at specific stages of ..
  45. Park J, Shin M, Lambert P. High incidence of female reproductive tract cancers in FA-deficient HPV16-transgenic mice correlates with E7's induction of DNA damage response, an activity mediated by E7's inactivation of pocket proteins. Oncogene. 2014;33:3383-91 pubmed publisher
    ..This hypothesis explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. ..
  46. Lachaud C, Slean M, Marchesi F, Lock C, Odell E, Castor D, et al. Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in Fan1 nuclease-defective knock-in mice. Genes Dev. 2016;30:639-44 pubmed publisher
    ..Thus, Fan1 nuclease activity promotes ICL repair in a manner that controls ploidy, a role that we show is not shared by the Fanconi anemia pathway or the Slx4-Slx1 nuclease also involved in ICL repair. ..
  47. Hemphill A, Bruun D, Thrun L, Akkari Y, Torimaru Y, Hejna K, et al. Mammalian SNM1 is required for genome stability. Mol Genet Metab. 2008;94:38-45 pubmed publisher
    ..lethality, not seen in either homozygous mutant alone, can be noted when the Snm1 disruption is combined with a Fancd2 disruption...
  48. Li X, Li J, Wilson A, Sipple J, Schick J, Pang Q. Fancd2 is required for nuclear retention of Foxo3a in hematopoietic stem cell maintenance. J Biol Chem. 2015;290:2715-27 pubmed publisher
    ..Here we show that the Fanconi anemia protein Fancd2 and stress transcriptional factor Foxo3a cooperate to prevent HSC exhaustion in mice...
  49. Kim M, Kim J. The role of USP1 autocleavage in DNA interstrand crosslink repair. FEBS Lett. 2016;590:340-8 pubmed publisher
    ..A critical step in this pathway is mono-ubiquitination of FANCD2 (FANCD2-Ub). Deubiquitinase USP1 removes ubiquitin from FANCD2 resulting in inactivation of the FA pathway...