Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells

M. A. Siddique, K. Nakanishi, T. Taniguchi, Markus Grompe, A. D. D'Andrea

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

ObjectiveFanconi anemia (FA) is a human autosomal-recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to mitomycin C (MMC). FA has at least eight complementation groups (A, B, C, D1, D2, E, F, G), and six of the FA genes have been cloned. Several FA proteins, including FANCA, FANCC, FANCF, and FANCG, interact in a nuclear complex, and this complex is required for the activation (monoubiquitination) of the downstream FANCD2 protein. Activation of FANCD2 results in the assembly of FANCD2/BRCA1 foci. The aim of this study was to analyze the FA pathway in several FA patient-derived cell lines.Materials and MethodsWe generated an antibody to FANCF and analyzed FANCF expression in human lymphoblasts corresponding to all known FA subtypes. We systematically analyzed the FA pathway (FANCD2 monoubiquitination and assembly of FANCD2 nuclear foci) in patient-derived FA-F and FA-D1 cell lines.ResultsFANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary during cell cycle progression. FANCF, but not FANCD2, is a component of the nuclear FA protein complex and appears to stabilize other subunits of the complex. FANCF is required for the monoubiquitination of the FANCD2 protein following ionizing radiation. FANCD2 is monoubiquitinated in FA-D1 cells, even though these cells are highly sensitive to MMC.ConclusionsThe recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway.

Original languageEnglish (US)
Pages (from-to)1448-1455
Number of pages8
JournalExperimental Hematology
Volume29
Issue number12
DOIs
StatePublished - 2001

Fingerprint

Fanconi Anemia
Fanconi Anemia Complementation Group D2 Protein
Mitomycin
Fanconi Anemia Complementation Group F Protein
Fanconi Anemia Complementation Group A Protein
BRCA2 Protein
Multiple Abnormalities
Cell Line
Nuclear Proteins
Ionizing Radiation
Anemia
Cell Cycle
Bone Marrow
Antibodies
Genes
Complementation Group D1 Fanconi Anemia
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. / Siddique, M. A.; Nakanishi, K.; Taniguchi, T.; Grompe, Markus; D'Andrea, A. D.

In: Experimental Hematology, Vol. 29, No. 12, 2001, p. 1448-1455.

Research output: Contribution to journalArticle

Siddique, M. A. ; Nakanishi, K. ; Taniguchi, T. ; Grompe, Markus ; D'Andrea, A. D. / Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. In: Experimental Hematology. 2001 ; Vol. 29, No. 12. pp. 1448-1455.
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abstract = "ObjectiveFanconi anemia (FA) is a human autosomal-recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to mitomycin C (MMC). FA has at least eight complementation groups (A, B, C, D1, D2, E, F, G), and six of the FA genes have been cloned. Several FA proteins, including FANCA, FANCC, FANCF, and FANCG, interact in a nuclear complex, and this complex is required for the activation (monoubiquitination) of the downstream FANCD2 protein. Activation of FANCD2 results in the assembly of FANCD2/BRCA1 foci. The aim of this study was to analyze the FA pathway in several FA patient-derived cell lines.Materials and MethodsWe generated an antibody to FANCF and analyzed FANCF expression in human lymphoblasts corresponding to all known FA subtypes. We systematically analyzed the FA pathway (FANCD2 monoubiquitination and assembly of FANCD2 nuclear foci) in patient-derived FA-F and FA-D1 cell lines.ResultsFANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary during cell cycle progression. FANCF, but not FANCD2, is a component of the nuclear FA protein complex and appears to stabilize other subunits of the complex. FANCF is required for the monoubiquitination of the FANCD2 protein following ionizing radiation. FANCD2 is monoubiquitinated in FA-D1 cells, even though these cells are highly sensitive to MMC.ConclusionsThe recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway.",
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AU - Siddique, M. A.

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AU - Grompe, Markus

AU - D'Andrea, A. D.

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N2 - ObjectiveFanconi anemia (FA) is a human autosomal-recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to mitomycin C (MMC). FA has at least eight complementation groups (A, B, C, D1, D2, E, F, G), and six of the FA genes have been cloned. Several FA proteins, including FANCA, FANCC, FANCF, and FANCG, interact in a nuclear complex, and this complex is required for the activation (monoubiquitination) of the downstream FANCD2 protein. Activation of FANCD2 results in the assembly of FANCD2/BRCA1 foci. The aim of this study was to analyze the FA pathway in several FA patient-derived cell lines.Materials and MethodsWe generated an antibody to FANCF and analyzed FANCF expression in human lymphoblasts corresponding to all known FA subtypes. We systematically analyzed the FA pathway (FANCD2 monoubiquitination and assembly of FANCD2 nuclear foci) in patient-derived FA-F and FA-D1 cell lines.ResultsFANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary during cell cycle progression. FANCF, but not FANCD2, is a component of the nuclear FA protein complex and appears to stabilize other subunits of the complex. FANCF is required for the monoubiquitination of the FANCD2 protein following ionizing radiation. FANCD2 is monoubiquitinated in FA-D1 cells, even though these cells are highly sensitive to MMC.ConclusionsThe recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway.

AB - ObjectiveFanconi anemia (FA) is a human autosomal-recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to mitomycin C (MMC). FA has at least eight complementation groups (A, B, C, D1, D2, E, F, G), and six of the FA genes have been cloned. Several FA proteins, including FANCA, FANCC, FANCF, and FANCG, interact in a nuclear complex, and this complex is required for the activation (monoubiquitination) of the downstream FANCD2 protein. Activation of FANCD2 results in the assembly of FANCD2/BRCA1 foci. The aim of this study was to analyze the FA pathway in several FA patient-derived cell lines.Materials and MethodsWe generated an antibody to FANCF and analyzed FANCF expression in human lymphoblasts corresponding to all known FA subtypes. We systematically analyzed the FA pathway (FANCD2 monoubiquitination and assembly of FANCD2 nuclear foci) in patient-derived FA-F and FA-D1 cell lines.ResultsFANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary during cell cycle progression. FANCF, but not FANCD2, is a component of the nuclear FA protein complex and appears to stabilize other subunits of the complex. FANCF is required for the monoubiquitination of the FANCD2 protein following ionizing radiation. FANCD2 is monoubiquitinated in FA-D1 cells, even though these cells are highly sensitive to MMC.ConclusionsThe recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway.

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