The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG

Johan P. De Winter, Laura Van Der Weel, Jan De Groot, Stacie Stone, Quinten Waisfisz, Fré Arwert, Rik J. Scheper, Frank A E Kruyt, Maureen Hoatlin, Hans Joenje

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Fanconi anemia (FA) is a chromosomal instability syndrome associated with a strong predisposition to cancer, particularly acute myeloid leukemia and squamous cell carcinoma. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. Complementation analysis has indicated that at least seven distinct genes are involved in the pathogenesis of FA. Despite the identification of four of these genes (FANCA, FANCC, FANCF and FANCG), the nature of the 'FA pathway' has remained enigmatic, as the FA proteins lack sequence homologies or motifs that could point to a molecular function. To further define this pathway, we studied the subcellular localizations and mutual interactions of the FA proteins, including the recently identified FANCF protein, in human lymphoblasts. FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. These interactions were detected in wild-type and FA-D lymphoblasts, but not in lymphoblasts of other FA complementation groups. This implies that each of the FA proteins, except FANCD, is required for these complexes to form. Similarly, we show that the interaction between FANCA and FANCC is restricted to wild-type and FA-D cells. Furthermore, we document the subcellular localization of FANCA and the FANCA/FANCG complex in all FA complementation groups. Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity.

Original languageEnglish (US)
Pages (from-to)2665-2674
Number of pages10
JournalHuman Molecular Genetics
Volume9
Issue number18
StatePublished - Nov 1 2000

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Fanconi Anemia Complementation Group Proteins
Fanconi Anemia
Amino Acid Sequence Homology
Chromosome Breakage
Chromosomal Instability
Somatostatin-Secreting Cells
Myeloid Cells
Acute Myeloid Leukemia
Genes
Squamous Cell Carcinoma
Hypersensitivity

ASJC Scopus subject areas

  • Genetics

Cite this

De Winter, J. P., Van Der Weel, L., De Groot, J., Stone, S., Waisfisz, Q., Arwert, F., ... Joenje, H. (2000). The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Human Molecular Genetics, 9(18), 2665-2674.

The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. / De Winter, Johan P.; Van Der Weel, Laura; De Groot, Jan; Stone, Stacie; Waisfisz, Quinten; Arwert, Fré; Scheper, Rik J.; Kruyt, Frank A E; Hoatlin, Maureen; Joenje, Hans.

In: Human Molecular Genetics, Vol. 9, No. 18, 01.11.2000, p. 2665-2674.

Research output: Contribution to journalArticle

De Winter, JP, Van Der Weel, L, De Groot, J, Stone, S, Waisfisz, Q, Arwert, F, Scheper, RJ, Kruyt, FAE, Hoatlin, M & Joenje, H 2000, 'The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG', Human Molecular Genetics, vol. 9, no. 18, pp. 2665-2674.
De Winter JP, Van Der Weel L, De Groot J, Stone S, Waisfisz Q, Arwert F et al. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Human Molecular Genetics. 2000 Nov 1;9(18):2665-2674.
De Winter, Johan P. ; Van Der Weel, Laura ; De Groot, Jan ; Stone, Stacie ; Waisfisz, Quinten ; Arwert, Fré ; Scheper, Rik J. ; Kruyt, Frank A E ; Hoatlin, Maureen ; Joenje, Hans. / The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 18. pp. 2665-2674.
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AU - Stone, Stacie

AU - Waisfisz, Quinten

AU - Arwert, Fré

AU - Scheper, Rik J.

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