FANCI

Summary

Gene Symbol: FANCI
Description: Fanconi anemia complementation group I
Alias: KIAA1794, Fanconi anemia group I protein
Species: human
Products:     FANCI

Top Publications

  1. Dorsman J, Levitus M, Rockx D, Rooimans M, Oostra A, Haitjema A, et al. Identification of the Fanconi anemia complementation group I gene, FANCI. Cell Oncol. 2007;29:211-8 pubmed
    ..We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I...
  2. 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
    ..Here we describe the FA protein FANCI, identified as an ATM/ATR kinase substrate required for resistance to mitomycin C...
  3. 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
    ..Furthermore, addition of the FANCI protein enhances monoubiquitination and also restricts it to the in vivo substrate lysine residue on FANCD2...
  4. MacKay C, Déclais A, Lundin C, Agostinho A, Deans A, MacArtney T, et al. Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell. 2010;142:65-76 pubmed publisher
    ..Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair. ..
  5. Colnaghi L, Jones M, Cotto Rios X, Schindler D, Hanenberg H, Huang T. Patient-derived C-terminal mutation of FANCI causes protein mislocalization and reveals putative EDGE motif function in DNA repair. Blood. 2011;117:2247-56 pubmed publisher
    ..pathway requires the FA core ubiquitin ligase complex-dependent monoubiquitination of 2 interacting FA proteins, FANCI and FANCD2...
  6. Hodson C, Cole A, Lewis L, Miles J, Purkiss A, Walden H. Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway. J Biol Chem. 2011;286:32628-37 pubmed publisher
    ..At the heart of this pathway is the monoubiquitination of the FANCI-FANCD2 (ID) complex by the multiprotein "core complex" containing the E3 ubiquitin ligase FANCL...
  7. 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
    ..or replication fork stress, the Fanconi anemia pathway is activated, leading to monoubiquitination of FANCD2 and FANCI and their colocalization in foci...
  8. Moldovan G, Madhavan M, Mirchandani K, McCaffrey R, Vinciguerra P, D Andrea A. DNA polymerase POLN participates in cross-link repair and homologous recombination. Mol Cell Biol. 2010;30:1088-96 pubmed publisher
    ..Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links. ..
  9. Rego M, Kolling F, Vuono E, Mauro M, Howlett N. Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the FANCD2 protein. Blood. 2012;120:2109-17 pubmed publisher
    ..A key step in FA-BRCA pathway activation is the covalent attachment of monoubiquitin to FANCD2 and FANCI. Monoubiquitinated FANCD2 and FANCI localize in chromatin-associated nuclear foci where they interact with several ..

More Information

Publications104 found, 100 shown here

  1. 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
    ..These complexes appear to be required for normal homology-directed DNA repair. ..
  2. Yuan F, El Hokayem J, Zhou W, Zhang Y. FANCI protein binds to DNA and interacts with FANCD2 to recognize branched structures. J Biol Chem. 2009;284:24443-52 pubmed publisher
    In this study, we report that the purified wild-type FANCI (Fanconi anemia complementation group I) protein directly binds to a variety of DNA substrates...
  3. Longerich S, San Filippo J, Liu D, Sung P. FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. J Biol Chem. 2009;284:23182-6 pubmed publisher
    b>FANCI is integral to the Fanconi anemia (FA) pathway of DNA damage repair...
  4. Liu T, Ghosal G, Yuan J, Chen J, Huang J. FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science. 2010;329:693-6 pubmed publisher
    ..A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex...
  5. Shigechi T, Tomida J, Sato K, Kobayashi M, Eykelenboom J, Pessina F, et al. ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway. Cancer Res. 2012;72:1149-56 pubmed publisher
    ..This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby ..
  6. Sato K, Toda K, Ishiai M, Takata M, Kurumizaka H. DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI. Nucleic Acids Res. 2012;40:4553-61 pubmed publisher
    b>FANCI and FANCD2 form a complex, and play essential roles in the repair of interstrand DNA crosslinks (ICLs) by the Fanconi anemia (FA) pathway...
  7. Longerich S, Kwon Y, Tsai M, Hlaing A, Kupfer G, Sung P. Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA. Nucleic Acids Res. 2014;42:5657-70 pubmed publisher
    FANCD2 and FANCI function together in the Fanconi anemia network of deoxyribonucleic acid (DNA) crosslink repair...
  8. Unno J, Itaya A, Taoka M, Sato K, Tomida J, Sakai W, et al. FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair. Cell Rep. 2014;7:1039-47 pubmed publisher
    ..Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair...
  9. 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
    ..A FANCD2 protein sequence-based homology search facilitated the discovery of FANCI, a second monoubiquitinated component of the FA pathway...
  10. Tremblay C, Huang F, Levesque G, Carreau M. Fanconi anemia core complex-dependent HES1 mono-ubiquitination regulates its transcriptional activity. BMC Res Notes. 2018;11:138 pubmed publisher
    ..products form a nuclear core complex containing E3 ligase activity required for mono-ubiquitination of FANCD2 and FANCI, both of which are FA proteins...
  11. Geng L, Huntoon C, Karnitz L. RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network. J Cell Biol. 2010;191:249-57 pubmed publisher
    ..A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase...
  12. Liang Z, Liang F, Teng Y, Chen X, Liu J, Longerich S, et al. Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination. Cell Rep. 2019;26:564-572.e5 pubmed publisher
    ..We further demonstrate that highly purified human FANCI-FANCD2 (ID2) complex binds synthetic single-stranded RNA (ssRNA) and R-loop substrates with high affinity, ..
  13. Yu L, Ke J, Du X, Yu Z, Gao D. Genetic characterization of thymoma. Sci Rep. 2019;9:2369 pubmed publisher
    ..Interestingly, among these genes upregulated more than 2-fold, 6 driver genes (FANCI, NCAPD3, NCAPG, OXCT1, EPHA1 and MCM2) were formerly reported as driver oncogenes...
  14. Chaugule V, Arkinson C, Toth R, Walden H. Enzymatic preparation of monoubiquitinated FANCD2 and FANCI proteins. Methods Enzymol. 2019;618:73-104 pubmed publisher
    ..At the heart of this pathway lies the monoubiquitination of FANCD2 and FANCI proteins, which triggers the recruitment of DNA repair factors...
  15. Bouffard F, Plourde K, Bélanger S, Ouellette G, Labrie Y, Durocher F. Analysis of a FANCE Splice Isoform in Regard to DNA Repair. J Mol Biol. 2015;427:3056-73 pubmed publisher
    ..In addition, FANCEΔ4 did not allow FANCD2 and FANCI monoubiquitination, which represents a crucial step of the FANC-BRCA functional pathway...
  16. 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...
  17. Mason J, Sekiguchi J. Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks. Hum Mol Genet. 2011;20:2549-59 pubmed publisher
    ..cells, and this phenotype is not further exacerbated upon depletion of either FANCD2 or another key FA protein, FANCI. Furthermore, we find that SNM1B is required for proper localization of critical repair factors, including FANCD2, ..
  18. Cole A, Lewis L, Walden H. The structure of the catalytic subunit FANCL of the Fanconi anemia core complex. Nat Struct Mol Biol. 2010;17:294-8 pubmed publisher
    ..anemia (FA) pathway is activated in response to DNA damage, leading to monoubiquitination of the substrates FANCI and FANCD2 by the FA core complex...
  19. Paulo P, Maia S, Pinto C, Pinto P, Monteiro A, Peixoto A, et al. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer. PLoS Genet. 2018;14:e1007355 pubmed publisher
    ..new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4...
  20. Bonache S, Esteban I, Moles Fernández A, Tenés A, Duran Lozano L, Montalban G, et al. Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. J Cancer Res Clin Oncol. 2018;144:2495-2513 pubmed publisher
    ..variants were detected in candidate BC/OC genes in 17 patients (1 BARD1, 1 ERCC3, 1 ERCC5, 2 FANCE, 1 FANCI, 2 FANCL, 1 FANCM, 1 MCPH1, 1 PPM1D, 2 RBBP8, 3 RECQL4 and 1 with SLX4 and XRCC2), three of which also carry ..
  21. Wang H, Li S, Oaks J, Ren J, Li L, Wu X. The concerted roles of FANCM and Rad52 in the protection of common fragile sites. Nat Commun. 2018;9:2791 pubmed publisher
    ..of Fanconi anemia (FA) protein FANCM in the protection of CFSs that is independent of the FA core complex and the FANCI-FANCD2 complex...
  22. Stolk L, Perry J, Chasman D, He C, Mangino M, Sulem P, et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat Genet. 2012;44:260-8 pubmed publisher
    ..genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2))...
  23. Herrmann N, Knoll A, Puchta H. The nuclease FAN1 is involved in DNA crosslink repair in Arabidopsis thaliana independently of the nuclease MUS81. Nucleic Acids Res. 2015;43:3653-66 pubmed publisher
    ..essential step in CL repair is the activation of the pathway by the monoubiquitination of the heterodimer FANCD2/FANCI, which recruits the nuclease FAN1 to the CL site...
  24. Lin P, Kuo W, Huang A, Lu Y, Lin C, Kuo S, et al. Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer. Oncotarget. 2016;7:8310-20 pubmed publisher
    ..carry germline deleterious mutations, 9 in BRCA1, 11 in BRCA2, 2 in RAD50, 2 in TP53 and one each in ATM, BRIP1, FANCI, MSH2, MUTYH, and RAD51C. Triple-negative breast cancer (TNBC) was associated with the highest mutation rate (45...
  25. Sung P, Wen K, Chen Y, Chao T, Tsai Y, Tseng L, et al. The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels. PLoS ONE. 2017;12:e0185615 pubmed publisher
    ..The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53...
  26. Liang C, Li Z, Lopez Martinez D, Nicholson W, Venien Bryan C, Cohn M. The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2. Nat Commun. 2016;7:12124 pubmed publisher
    The Fanconi anaemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination...
  27. Semlow D, Zhang J, Budzowska M, Drohat A, Walter J. Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3 Glycosylase. Cell. 2016;167:498-511.e14 pubmed publisher
    ..In vertebrates, ICL repair is triggered when replication forks collide with the lesion, leading to FANCI-FANCD2-dependent unhooking and formation of a double-strand break (DSB) intermediate...
  28. Isaacsson Velho P, Qazi F, Hassan S, Carducci M, Denmeade S, Markowski M, et al. Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects. Eur Urol. 2018;: pubmed publisher
    ..7%) had a germline/somatic HRD mutation (three in BRCA2, and one each in ATM, ATR, CHEK2, FANCG, FANCI, FANCL, and PALB2) and 18 (64.3%) did not...
  29. 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
    ..syndrome with at least 13 complementation groups (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and FANCN)...
  30. Ishiai M, Sato K, Tomida J, Kitao H, Kurumizaka H, Takata M. Activation of the FA pathway mediated by phosphorylation and ubiquitination. Mutat Res. 2017;803-805:89-95 pubmed publisher
    ..activated upon ICL damage, and a hallmark of this activation is the mono-ubiquitination events of the key FANCD2-FANCI protein complex...
  31. Jin H, Roy U, Lee G, SCHARER O, Cho Y. Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease. J Biol Chem. 2018;293:6482-6496 pubmed publisher
    ..FANCD2-FANCI-associated nuclease (FAN1) is a conserved structure-specific nuclease that unhooks DNA ICLs independently of the ..
  32. Velimezi G, Robinson Garcia L, Muñoz Martínez F, Wiegant W, Ferreira da Silva J, Owusu M, et al. Map of synthetic rescue interactions for the Fanconi anemia DNA repair pathway identifies USP48. Nat Commun. 2018;9:2280 pubmed publisher
    ..loss-of-function screens across a panel of human haploid isogenic FA-defective cells (FANCA, FANCC, FANCG, FANCI, FANCD2)...
  33. Gibbs Seymour I, Oka Y, Rajendra E, Weinert B, Passmore L, Patel K, et al. Ubiquitin-SUMO circuitry controls activated fanconi anemia ID complex dosage in response to DNA damage. Mol Cell. 2015;57:150-64 pubmed publisher
    We show that central components of the Fanconi anemia (FA) DNA repair pathway, the tumor suppressor proteins FANCI and FANCD2 (the ID complex), are SUMOylated in response to replication fork stalling...
  34. Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinková P, Luo Z, et al. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. 2011;25:2158-72 pubmed publisher
    ..BRCA1 (breast and ovarian cancer type 1 susceptibility protein 1), ATR (ataxia telangiectasia and Rad3-related), FANCI, and FANCD2. We show that CycK/Cdk12, rather than CycK/Cdk13, is necessary for their expression...
  35. Budzowska M, Graham T, Sobeck A, Waga S, Walter J. Regulation of the Rev1-pol ζ complex during bypass of a DNA interstrand cross-link. EMBO J. 2015;34:1971-85 pubmed publisher
    ..Rev1-pol ζ recruitment requires the Fanconi anemia core complex but not FancI-FancD2...
  36. Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, et al. Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia. Am J Hum Genet. 2015;96:1001-7 pubmed publisher
    ..The UBE2T E2 ubiquitin conjugating enzyme acts in FANCD2/FANCI monoubiquitination, a critical event in the pathway...
  37. Sato K, Shimomuki M, Katsuki Y, Takahashi D, Kobayashi W, Ishiai M, et al. FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. Nucleic Acids Res. 2016;44:10758-10771 pubmed
    The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive...
  38. Fritz S, Capitan A, Djari A, Rodriguez S, Barbat A, Baur A, et al. Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2. PLoS ONE. 2013;8:e65550 pubmed publisher
    ..Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein ..
  39. Vuono E, Mukherjee A, Vierra D, Adroved M, Hodson C, Deans A, et al. The PTEN phosphatase functions cooperatively with the Fanconi anemia proteins in DNA crosslink repair. Sci Rep. 2016;6:36439 pubmed publisher
    ..polyubiquitination and degradation, and the consequent inefficient assembly of the FA core complex, FANCD2, and FANCI into DNA repair foci...
  40. 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...
  41. Osborn M, Lonetree C, Webber B, Patel D, Dunmire S, McElroy A, et al. CRISPR/Cas9 Targeted Gene Editing and Cellular Engineering in Fanconi Anemia. Stem Cells Dev. 2016;25:1591-1603 pubmed
    ..we employed footprint free reprogramming of fibroblasts from a patient with mutations to the Fanconi anemia I (FANCI) gene to generate induced pluripotent stem cells (iPSC)...
  42. Betti M, Casalone E, Ferrante D, Aspesi A, Morleo G, Biasi A, et al. Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma. Cancer Lett. 2017;405:38-45 pubmed publisher
    ..Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC...
  43. Vierra D, Garzon J, Rego M, Adroved M, Mauro M, Howlett N. Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure. Oncotarget. 2017;8:76443-76457 pubmed publisher
    ..A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci...
  44. 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 ..
  45. Chan K, Palmai Pallag T, Ying S, Hickson I. Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol. 2009;11:753-60 pubmed publisher
    ..Here we show that the Fanconi anaemia proteins FANCD2 and FANCI specifically associate with common fragile site loci irrespective of whether the chromosome is broken...
  46. Seguí N, Mina L, Lázaro C, Sanz Pamplona R, Pons T, Navarro M, et al. Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair. Gastroenterology. 2015;149:563-6 pubmed publisher
    ..These individuals had mismatch repair-proficient tumors and each carried nonsense variant in the FANCD2/FANCI-associated nuclease 1 gene (FAN1), which encodes a nuclease involved in DNA inter-strand cross-link repair...
  47. Chen J, Rajasekaran M, Xia H, Zhang X, Kong S, Sekar K, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway. Gut. 2016;65:1522-34 pubmed publisher
    ..Thus, PRC1 controlled the expression and function of WRRAGs such as FANCI, SPC25, KIF11 and KIF23 via Wnt signalling...
  48. Tan W, Deans A. A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination. Exp Hematol. 2017;50:27-32 pubmed publisher
    ..Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins...
  49. Rickman K, Lach F, Abhyankar A, Donovan F, Sanborn E, Kennedy J, et al. Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia. Cell Rep. 2015;12:35-41 pubmed publisher
    ..component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following ..
  50. Swuec P, Renault L, Borg A, Shah F, Murphy V, van Twest S, et al. The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2. Cell Rep. 2017;18:611-623 pubmed publisher
    ..Activation of the main DNA interstrand crosslink repair pathway in higher eukaryotes requires mono-ubiquitination of FANCI and FANCD2 by FANCL, the E3 ligase subunit of the Fanconi anemia core complex...
  51. Thompson E, Yeo J, Lee E, Kan Y, Raghunandan M, Wiek C, et al. FANCI and FANCD2 have common as well as independent functions during the cellular replication stress response. Nucleic Acids Res. 2017;45:11837-11857 pubmed publisher
    ..hierarchy: following ICL detection on chromatin, the FA core complex monoubiquitinates and recruits the central FANCI and FANCD2 proteins that subsequently coordinate ICL removal and repair of the ensuing DNA double-stranded break ..
  52. Chan S, Lim W, Ishak N, Li S, Goh W, Tan G, et al. Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas. Sci Rep. 2017;7:10660 pubmed publisher
    ..predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53...
  53. Moder M, Velimezi G, Owusu M, Mazouzi A, Wiedner M, Ferreira da Silva J, et al. Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia. Nat Commun. 2017;8:1238 pubmed publisher
    ..FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the ..
  54. Mu J, Wang Y, Luo H, Leng M, Zhang J, Yang T, et al. A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints. J Biol Chem. 2007;282:17330-4 pubmed
  55. Williams S, Longerich S, Sung P, Vaziri C, Kupfer G. The E3 ubiquitin ligase RAD18 regulates ubiquitylation and chromatin loading of FANCD2 and FANCI. Blood. 2011;117:5078-87 pubmed publisher
    ..is the monoubiquitylation and chromatin localization of 2 FA proteins, FA complementation group D2 (FANCD2) and FANCI. In the present study, we show that RAD18 binds FANCD2 and is required for efficient monoubiquitylation and ..
  56. Savage S, Ballew B, Giri N, Chandrasekharappa S, Ameziane N, de Winter J, et al. Novel FANCI mutations in Fanconi anemia with VACTERL association. Am J Med Genet A. 2016;170A:386-391 pubmed publisher
    ..Autosomal recessive mutations in FANCI are a rare cause of FA...
  57. 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
    ..These findings demonstrate that FoxF1 is a key component of FA complexes and a critical mediator of DNA damage response in tumor cells. ..
  58. Lossaint G, Larroque M, Ribeyre C, Bec N, Larroque C, Décaillet C, et al. FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling. Mol Cell. 2013;51:678-90 pubmed publisher
    ..Upon replication stress signaling by ATR, the FA core complex monoubiquitinates FANCD2 and FANCI in order to activate DNA repair...
  59. Gwon G, Kim Y, Liu Y, Watson A, Jo A, Etheridge T, et al. Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1. Genes Dev. 2014;28:2276-90 pubmed publisher
    ..FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI-FANCD2 (ID) complex and participates in ICL repair...
  60. Renaudin X, Koch Lerner L, Menck C, Rosselli F. The ubiquitin family meets the Fanconi anemia proteins. Mutat Res Rev Mutat Res. 2016;769:36-46 pubmed publisher
    ..A key event in this pathway involves the monoubiquitination of the FANCD2-FANCI heterodimer by the collective action of at least 10 different proteins assembled in the FANC core complex...
  61. Cheung R, Castella M, Abeyta A, Gafken P, Tucker N, Taniguchi T. Ubiquitination-Linked Phosphorylation of the FANCI S/TQ Cluster Contributes to Activation of the Fanconi Anemia I/D2 Complex. Cell Rep. 2017;19:2432-2440 pubmed publisher
    ..crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination of the FANCI/FANCD2 (FANCI/D2) complex...
  62. Long D, R schle M, Joukov V, Walter J. Mechanism of RAD51-dependent DNA interstrand cross-link repair. Science. 2011;333:84-7 pubmed publisher
    ..Recombination acts downstream of FANCI-FANCD2, yet RAD51 binds ICL-stalled replication forks independently of FANCI-FANCD2 and before DSB formation...
  63. Yang K, Moldovan G, Vinciguerra P, Murai J, Takeda S, D Andrea A. Regulation of the Fanconi anemia pathway by a SUMO-like delivery network. Genes Dev. 2011;25:1847-58 pubmed publisher
    ..How USP1/UAF1 is targeted to the FANCD2/FANCI heterodimer has remained unknown...
  64. Takahashi D, Sato K, Shimomuki M, Takata M, Kurumizaka H. Expression and purification of human FANCI and FANCD2 using Escherichia coli cells. Protein Expr Purif. 2014;103:8-15 pubmed publisher
    ..In higher eukaryotes, the Fanconi anemia proteins, FANCI and FANCD2, form a heterodimer and play essential roles in ICL repair...
  65. Swuec P, Costa A. DNA replication and inter-strand crosslink repair: Symmetric activation of dimeric nanomachines?. Biophys Chem. 2017;225:15-19 pubmed publisher
    ..of a set of DNA-processing factors onto a dimeric protein complex, which functions as a loading platform (MCM and FANCI-FANCD2 respectively)...
  66. Siddiqui M, Rajpurohit Y, Thapa P, Maurya G, Banerjee K, Khan M, et al. Studies of protein-protein interactions in Fanconi anemia pathway to unravel the DNA interstrand crosslink repair mechanism. Int J Biol Macromol. 2017;104:1338-1344 pubmed publisher
    ..A set of FA pathway proteins mainly FANCI, FANCD2 and BRCA2 are expressed to repair the covalent crosslink between the dsDNA...
  67. Castella M, Jacquemont C, Thompson E, Yeo J, Cheung R, Huang J, et al. FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. PLoS Genet. 2015;11:e1005563 pubmed publisher
    ..ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex). However, the regulation of the FA core complex itself is poorly understood...
  68. 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
    ..exposure 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...
  69. Chen Y, Jones M, Yin Y, Crist S, Colnaghi L, Sims R, et al. ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress. Mol Cell. 2015;58:323-38 pubmed publisher
    ..Herein, we identify a member of the Fanconi anemia (FA) DNA repair pathway, FANCI, as a key effector of dormant origin firing in response to replication stress...
  70. Yang Y, Liu Z, Wang F, Temviriyanukul P, Ma X, Tu Y, et al. FANCD2 and REV1 cooperate in the protection of nascent DNA strands in response to replication stress. Nucleic Acids Res. 2015;43:8325-39 pubmed publisher
    ..Collectively these data suggest that REV1 plays multiple roles at stalled replication forks in response to replication stress. ..
  71. Cohn M, Kowal P, Yang K, Haas W, Huang T, Gygi S, et al. A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway. Mol Cell. 2007;28:786-97 pubmed
    ..Taken together, our results describe a mechanism of regulation of the deubiquitinating enzyme, USP1, and of DNA repair. ..
  72. Barroso E, Pita G, Arias J, Menendez P, Zamora P, Blanco M, et al. The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features. Breast Cancer Res Treat. 2009;118:655-60 pubmed publisher
    ..Sub-group analyses revealed associations between SNPs on FANCI and ATM and nodal metastasis status and between FANCJ/BRIP1 and FANCN/PALB2 and PR- status.
  73. Garcia M, Fernandez V, Osorio A, Barroso A, Fernandez F, Urioste M, et al. Mutational analysis of FANCL, FANCM and the recently identified FANCI suggests that among the 13 known Fanconi Anemia genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition. Carcinogenesis. 2009;30:1898-902 pubmed publisher
    ..in breast cancer families negative for BRCA1/2 mutations but the role of FANCL, FANCM and the recently identified FANCI has not been evaluated to date...
  74. Sato K, Ishiai M, Takata M, Kurumizaka H. Defective FANCI binding by a fanconi anemia-related FANCD2 mutant. PLoS ONE. 2014;9:e114752 pubmed publisher
    ..FANCD2 forms a complex with FANCI (ID complex) and is monoubiquitinated, which facilitates the downstream interstrand crosslink (ICL) repair steps, ..
  75. Liang F, Longerich S, Miller A, Tang C, Buzovetsky O, Xiong Y, et al. Promotion of RAD51-Mediated Homologous DNA Pairing by the RAD51AP1-UAF1 Complex. Cell Rep. 2016;15:2118-2126 pubmed publisher
    ..Our findings provide insights into an apparently USP1-independent role of UAF1 in genome maintenance. ..
  76. Bretscher H, Fox D. Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2. Dev Cell. 2016;37:444-57 pubmed publisher
    ..To survive mitosis with acentric chromosomes, papillar cells require Fanconi anemia proteins FANCD2 and FANCI, as well as Blm helicase, but not canonical DDR signaling...
  77. Bhattacharjee S, Nandi S. DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun Signal. 2017;15:41 pubmed publisher
    ..signaling network contains a unique nuclear protein complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, ..
  78. Oka Y, Bekker Jensen S, Mailand N. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. EMBO J. 2015;34:1385-98 pubmed publisher
    ..of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI ..
  79. Bick G, Zhang F, Meetei A, Andreassen P. Coordination of the recruitment of the FANCD2 and PALB2 Fanconi anemia proteins by an ubiquitin signaling network. Chromosoma. 2017;126:417-430 pubmed publisher
    ..These two arms include the upstream FA pathway, which culminates in the monoubiquitination of FANCD2 and FANCI, and downstream breast cancer (BRCA)-associated proteins that interact in protein complexes...
  80. van Twest S, Murphy V, Hodson C, Tan W, Swuec P, O Rourke J, et al. Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway. Mol Cell. 2017;65:247-259 pubmed publisher
    Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA)...
  81. Wang X, Zhang X, Peng L, Liu Z, Yang Y, He Z, et al. Bardoxolone methyl (CDDO-Me or RTA402) induces cell cycle arrest, apoptosis and autophagy via PI3K/Akt/mTOR and p38 MAPK/Erk1/2 signaling pathways in K562 cells. Am J Transl Res. 2017;9:4652-4672 pubmed
    ..A total of 1,555 proteins responded to CDDO-Me exposure, including FANCI, SRPK2, XPO5, HP1BP3, NELFCD, Na+,K+-ATPase 1, etc. in K562 cells...
  82. Boisvert R, Rego M, Azzinaro P, Mauro M, Howlett N. Coordinate nuclear targeting of the FANCD2 and FANCI proteins via a FANCD2 nuclear localization signal. PLoS ONE. 2013;8:e81387 pubmed publisher
    ..A central step in the activation of this pathway is the monoubiquitination of the FANCD2 and FANCI proteins...
  83. Wang C, Krishnan V, Tay L, Chin D, Koh C, Chooi J, et al. Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia predisposition due to transcriptional and DNA repair defects. Cell Rep. 2014;8:767-82 pubmed publisher
    ..These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes the development of leukemias and other cancers. ..
  84. Airik R, Schueler M, Airik M, Cho J, Porath J, Mukherjee E, et al. A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis. J Am Soc Nephrol. 2016;27:3552-3559 pubmed
    ..We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans...
  85. Zhang X, Lu X, Akhter S, Georgescu M, Legerski R. FANCI is a negative regulator of Akt activation. Cell Cycle. 2016;15:1134-43 pubmed publisher
    ..We report here the existence of a novel protein complex that is composed minimally of Akt, PHLPP1, PHLPP2, FANCI, FANCD2, USP1 and UAF1...
  86. Siddiqui M, Choudhary R, Thapa P, Kulkarni N, Rajpurohit Y, Misra H, et al. Structural and biophysical properties of h-FANCI ARM repeat protein. J Biomol Struct Dyn. 2017;35:3032-3042 pubmed publisher
    Fanconi anemia complementation groups - I (FANCI) protein facilitates DNA ICL (Inter-Cross-link) repair and plays a crucial role in genomic integrity...
  87. Jin H, Cho Y. Structural and functional relationships of FAN1. DNA Repair (Amst). 2017;56:135-143 pubmed publisher
    FANCD2/FANCI-associated nuclease (FAN1) is a 5' flap structure-specific endonuclease and 5' to 3' exonuclease...
  88. Moriel Carretero M, Ovejero S, Gérus Durand M, Vryzas D, Constantinou A. Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors. J Cell Biol. 2017;216:4007-4026 pubmed publisher
    ..Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ..
  89. 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. ..
  90. Levitus M, Rooimans M, Steltenpool J, Cool N, Oostra A, Mathew C, et al. Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes. Blood. 2004;103:2498-503 pubmed
    ..Our results suggest that the FA pathway of genome stabilization may be controlled by at least 11 different genes, including FANCI and FANCJ.