Research Topics
Genomes and Genes
| ALAN D D'ANDREASummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Targeting DNA repair pathways in AMLALAN D D'ANDREA
Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Best Pract Res Clin Haematol 23:469-73. 2010..Biomarkers in the Fanconi anemia repair pathway may provide a predictor to identify this subset of patients who are sensitive to this new class of drugs...- BRCA1: a missing link in the Fanconi anemia/BRCA pathwayALAN D D'ANDREA
Departments of Radiation Oncology and Pediatrics, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
Cancer Discov 3:376-8. 2013..Interestingly, the woman had validated germline mutations in both BRCA1 alleles. These findings further implicate BRCA1 in the Fanconi anemia/BRCA pathway and have important implications for BRCA1 genetic testing... 
CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumorsClark C Chen
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Mol Cancer 8:24. 2009..These observations suggest that DNA repair deficient tumors should exhibit increased sensitivity to CHK1 inhibition. Here we offer experimental evidence in support of this hypothesis...
The Fanconi anaemia/BRCA pathwayALAN D D'ANDREA
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
Nat Rev Cancer 3:23-34. 2003..Recent studies implicate the FA proteins in the process of repairing chromosome defects that occur during homologous recombination, and disruption of the FA genes results in chromosome instability--a common feature of many human cancers...- The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin-sensitive ovarian cancersALAN D D'ANDREA
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
Cell Cycle 2:290-2. 2003..The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers... - Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistanceGary P H Ho
Dana Farber Cancer Institute, Department of Radiation Oncology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Mol Cell Biol 26:7005-15. 2006..These findings further support the functional connection of ATM/ATR kinases and FANCD2 in the DNA damage response and support a role for the FA pathway in the coordination of the S phase of the cell cycle... - Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatinRocio Montes De Oca
Dana Farber Cancer Institute, Department of Radiation Oncology, Harvard Medical School, 44 Binney St, Boston, MA 02115, USA
Blood 105:1003-9. 2005..We hypothesize that the carboxy terminus of FANCD2-44 plays a critical role in sensing or repairing DNA damage... - Regulation of monoubiquitinated PCNA by DUB autocleavageTony T Huang
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Nat Cell Biol 8:339-47. 2006..Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB... - WDR20 regulates activity of the USP12 x UAF1 deubiquitinating enzyme complexYounghoon Kee
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Biol Chem 285:11252-7. 2010..We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1 x USP complexes... - Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24Jung Min Kim
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Blood 111:5215-22. 2008..Dysregulated loading of the FA core complex accounts, at least in part, for the characteristic cellular and developmental abnormalities in FA... - UAF1 is a subunit of multiple deubiquitinating enzyme complexesMartin A Cohn
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 284:5343-51. 2009..We postulate that additional WD40-containing proteins may also form complexes with other human deubiquitinating enzymes and thereby regulate their activity and substrate specificity... - Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutatedRichard D Kennedy
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
J Clin Invest 117:1440-9. 2007..Pharmaceutical inhibition of ATM may have a role in the treatment of FA pathway-deficient human cancers... - DNA polymerase POLN participates in cross-link repair and homologous recombinationGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02215, USA
Mol Cell Biol 30:1088-96. 2010..Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links... - Interaction of FANCD2 and NBS1 in the DNA damage responseKoji Nakanishi
Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Nat Cell Biol 4:913-20. 2002..NBS1 and FANCD2 therefore cooperate in two distinct cellular functions, one involved in the DNA crosslink response and one involved in the S-phase checkpoint response... - Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complexPrzemyslaw Kowal
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 282:2047-55. 2007..FANCF mutants bearing amino acid substitutions in this C-terminal surface fail to interact with other components of the FA complex, indicating that this surface is critical for the proper assembly of the FA core complex... - Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathwayXiaoZhe Wang
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Mol Cell Biol 27:3098-108. 2007..Chk1-mediated phosphorylation of FANCE is required for a function independent of FANCD2 monoubiquitination... - S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51Toshiyasu Taniguchi
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Blood 100:2414-20. 2002.... - RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc fingerKailin Yang
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 285:19085-91. 2010..Taken together, our results identify a novel RAD18-PCNA(Ub)-SNM1A pathway required for nuclear focus formation and ICL resistance... - Human MutS and FANCM complexes function as redundant DNA damage sensors in the Fanconi Anemia pathwayMin Huang
Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, United States
DNA Repair (Amst) 10:1203-12. 2011..Further, MSH2 was co-purified and co-immunoprecipitated with FA core complex components. Taken together, our results suggest that human MutS homologs and FANCM complexes function as redundant DNA damage sensors of the FA pathway... - Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotypeJung Min Kim
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Dev Cell 16:314-20. 2009..Our results indicate that mouse Usp1 functions downstream in the FA pathway. Deubiquitination is a critical event required for Fancd2 nuclear foci assembly, release from chromatin, and function in DNA repair... - Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumorsToshiyasu Taniguchi
Department of Pediatric Oncology, Dana Farber Cancer Institute, Guy s King s and St Thomas School of Medicine, London, UK
Nat Med 9:568-74. 2003..We propose a model for ovarian tumor progression in which the initial methylation of FANCF is followed by FANCF demethylation and ultimately results in cisplatin resistance... - The WD40 repeats of FANCL are required for Fanconi anemia core complex assemblyAllan M Gurtan
Biological and Biomedical Sciences Program, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 281:10896-905. 2006..We propose a model in which FANCL, via its WD40 region, binds the FA complex and, via its PHD, recruits an as-yet-unidentified E2 for mono-ubiquitination of FANCD2... - Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatinXiaoZhe Wang
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 24:5850-62. 2004..These complexes appear to be required for normal homology-directed DNA repair... - Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damageNeil Johnson
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Mol Cell 35:327-39. 2009..Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function... - Regulation of the Fanconi anemia pathway by a SUMO-like delivery networkKailin Yang
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Genes Dev 25:1847-58. 2011..We propose that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and translesion DNA synthesis... - Inhibition of homologous recombination by the PCNA-interacting protein PARIGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Mol Cell 45:75-86. 2012..Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks... - The FANCM/FAAP24 complex is required for the DNA interstrand crosslink-induced checkpoint responseMin Huang
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 39:259-68. 2010..Therefore, we propose that FANCM/FAAP24 plays a role in ICL-induced checkpoint activation through regulating RPA recruiment at ICL-stalled replication forks... - Regulated degradation of FANCM in the Fanconi anemia pathway during mitosisYounghoon Kee
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 23:555-60. 2009..Nondegradable mutant forms of FANCM retain the FA core complex in the chromatin and disrupt the FA pathway. Our data provide a novel mechanism for the cell cycle-dependent regulation of the FA pathway... - ATR couples FANCD2 monoubiquitination to the DNA-damage responsePaul R Andreassen
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 18:1958-63. 2004.... - Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibitionNeil Johnson
Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
Nat Med 17:875-82. 2011..Because reduced Cdk1 activity impaired BRCA1 function and consequently, repair by homologous recombination, inhibition of Cdk1 represents a plausible strategy for expanding the utility of PARP inhibitors to BRCA-proficient cancers... - Regulation of Rev1 by the Fanconi anemia core complexHyungjin Kim
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
Nat Struct Mol Biol 19:164-70. 2012..We propose that the Fanconi anemia core complex regulates cross-link repair by channeling lesions to damage bypass pathways and preventing large DNA insertions and deletions... - A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathwayMartin A Cohn
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 28:786-97. 2007..Taken together, our results describe a mechanism of regulation of the deubiquitinating enzyme, USP1, and of DNA repair... - The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCCToshiyasu Taniguchi
Department of Pediatric Oncology, Dana Farber Cancer Institute, and the Department of Pediatrics, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Blood 100:2457-62. 2002..Our data indicate that FANCE is a component of the nuclear FA complex in vivo and is required for the monoubiquitination of FANCD2 and the downstream events in the FA pathway... - A novel diagnostic screen for defects in the Fanconi anemia pathwayAkiko Shimamura
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Blood 100:4649-54. 2002..A combination of retroviral gene transfer and FANCD2 immunoblotting provides a rapid subtyping assay for patients newly diagnosed with FA. These new FA screening assays would allow efficient testing of broad populations at risk... - Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cellsPatrizia Vinciguerra
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Clin Invest 120:3834-42. 2010..Based on these observations, we suggest that cytokinesis failure followed by apoptosis may contribute to bone marrow failure in patients with FA... - Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repairAgata Smogorzewska
Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Cell 129:289-301. 2007..Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I... - The Fanconi anemia core complex is required for efficient point mutagenesis and Rev1 foci assemblyKanchan D Mirchandani
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
DNA Repair (Amst) 7:902-11. 2008..Our results suggest a role for the FA core complex in regulating Rev1-dependent DNA damage tolerance independently of FANCD2, FANCI, and PCNA monoubiquitination... - FANCM: A landing pad for the Fanconi Anemia and Bloom's Syndrome complexesPatrizia Vinciguerra
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Mol Cell 36:916-7. 2009.... - Expanded roles of the Fanconi anemia pathway in preserving genomic stabilityYounghoon Kee
Department of Radiation Oncology and Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Genes Dev 24:1680-94. 2010..We also focus on the role of the FA pathway as a potential regulator of DNA repair choices in response to double-strand breaks, and its novel functions during the mitotic phase of the cell cycle... - Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosisTing Xi Liu
Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
Dev Cell 5:903-14. 2003.... - Chromatin recruitment of DNA repair proteins: lessons from the fanconi anemia and double-strand break repair pathwaysMartin A Cohn
Department of Radiation Oncology, Division of Genomic Stability and DNA Repair, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Mol Cell 32:306-12. 2008..Interestingly, these two pathways share several features, suggesting a more general mechanism for DNA-repair regulation... - Convergence of the fanconi anemia and ataxia telangiectasia signaling pathwaysToshiyasu Taniguchi
Department of Pediatric Oncology, Dana Farber Cancer Institute and Department of Pediatrics, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Cell 109:459-72. 2002..Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity... - Direct DNA binding activity of the Fanconi anemia D2 proteinWoo Hyun Park
Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:23593-8. 2005..This finding of DNA binding is the first biochemical activity identified for this key protein in the Fanconi anemia pathway... - The USP1/UAF1 complex promotes double-strand break repair through homologous recombinationJunko Murai
Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
Mol Cell Biol 31:2462-9. 2011..Disruption of NHEJ in UAF1-deficient cells restored cellular resistance to camptothecin and the PARP inhibitor. Our results indicate that the USP1/UAF1 complex promotes HR, at least in part by suppressing NHEJ... - Chromatin remodeling at DNA double-strand breaksBrendan D Price
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Cell 152:1344-54. 2013.... - Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathwayHyungjin Kim
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
Genes Dev 26:1393-408. 2012..Here, we review recent advances in our understanding of the downstream ICL repair steps initiated by ubiquitin-mediated FA pathway activation... - A DNA repair pathway-focused score for prediction of outcomes in ovarian cancer treated with platinum-based chemotherapyJosephine Kang
Harvard Radiation Oncology Program, Boston, MA, USA
J Natl Cancer Inst 104:670-81. 2012..We hypothesized that a molecular score based on expression of genes that are involved in platinum-induced DNA damage repair could provide such prognostic information... - Activation of Hif1α by the prolylhydroxylase inhibitor dimethyoxalyglycine decreases radiosensitivityMarina K Ayrapetov
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana Farber Cancer Institutes, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 6:e26064. 2011..Activation of Hif1α through prolylhydroxylase inhibition therefore identifies a new pathway for the development of novel radiation protectors... - DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancerBrian M Alexander
Dana Farber Brigham and Women s Cancer Center Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts, USA
Clin Cancer Res 16:5796-804. 2010.... - PARI Overexpression Promotes Genomic Instability and Pancreatic TumorigenesisKevin W O'Connor
Authors Affiliations Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts and Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
Cancer Res 73:2529-39. 2013..Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat PDAC. Cancer Res; 73(8); 2529-39. ©2013 AACR... - Biallelic inactivation of BRCA2 in Fanconi anemiaNiall G Howlett
Department of Pediatric Oncology, Children s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Science 297:606-9. 2002..Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations... - How the fanconi anemia pathway guards the genomeGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Annu Rev Genet 43:223-49. 2009.... - Stressed out: endogenous aldehydes damage hematopoietic stem cellsKalindi Parmar
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
Cell Stem Cell 11:583-4. 2012..Recently in Nature, Garaycoechea et al. (2012), identify aldehyde-mediated genotoxicity of hematopoietic stem cells as a cause for bone marrow failure... - To the rescue: the Fanconi anemia genome stability pathway salvages replication forksGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
Cancer Cell 22:5-6. 2012..In this issue of Cancer Cell, Schlacher et al. show that the Fanconi anemia and BRCA2 tumor suppressor pathways cooperate to protect stalled replication forks from degradation... - FANCD2 hurdles the DNA interstrand crosslinkGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Cell 139:1222-4. 2009..In a recent paper in Science, Knipscheer et al. (2009) demonstrate that the Fanconi Anemia protein FANCD2 promotes multiple steps of the crosslink repair process... - DNA damage discrimination at stalled replication forks by the Rad5 homologs HLTF and SHPRHGeorge Lucian Moldovan
Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02215, USA
Mol Cell 42:141-3. 2011..The results have important implications for the suppression of damage-specific mutagenesis and for the maintenance of genomic stability...
Research Grants
- Hematopoiesis by Ubiquitination and DeubiquitinationALAN D ANDREA; Fiscal Year: 2005..In the course of these experiments, we hope to determine novel protein regulators of in vivo hematopoietic stem cell growth and differentiation. ..
- Abnormalities/Signal Transduction/Hematopoietic DiseaseALAN D ANDREA; Fiscal Year: 2006..abstract_text> ..
- MOLECULAR PATHOGENESIS OF FANCONI ANEMIAALAN D ANDREA; Fiscal Year: 2003..For this specific aim, we will also test the nuclear FA protein complex for direct in vitro DNA binding activity or DNA repair activity, using model DNA templates. ..
- Core--Pilot grant programALAN D ANDREA; Fiscal Year: 2005..Resulting in new and immediately applicable medical and therapeutic response to radiation exposure. ..
- Regulation of the Fanconi Anemia Pathway by UbiquitinationALAN D ANDREA; Fiscal Year: 2007..Overall, we believe these studies will elucidate the cellular regulatory mechanisms which control the monoubiquitination state of key biological modulators, such as FANCD2. ..
- MOLECULAR PATHOGENESIS OF FANCONI ANEMIAALAN D ANDREA; Fiscal Year: 2007....
- STRUCTURE AND FUNCTION OF THE ERYTHROPOIETIN RECEPTORALAN D ANDREA; Fiscal Year: 1993..Other subunits of the EPO-R will be identified by crosslinking and coimmunoprecipitation, and various cloning strategies will be used to isolate the cDNAs encoding these other subunits...
- HEMATOPOIETIC CELL GROWTH AND DEUBIQUITINATING ENZYMESALAN D ANDREA; Fiscal Year: 2000..Finally, in Specific Aim #4, we will compare the enhancers of the DUB-I and DUB-2 gene for DNA sequences and binding proteins that determine the basis of cytokine-specific gene induction. ..
- Regulation of the Fanconi Anemia Pathway by UbiquitinationALAN DAVID D apos ANDREA; Fiscal Year: 2010..Overall, we believe these studies will elucidate the cellular regulatory mechanisms which control the monoubiquitination state of key biological modulators, such as FANCD2. ..