FANCE: the link between Fanconi anaemia complex assembly and activity

Pace, Paul E.; Johnson, Mark A.; Tan, Wu Meng; Mosedale, Georgina; Sng, Chelvin C. A.; Hoatlin, Maureen E.; Winter, Johan de; Joenje, Hans; Gergely, Fanni; Patel, Ketan

doi:10.1093/emboj/cdf355

Cited by 154 publications

(145 citation statements)

References 30 publications

(49 reference statements)

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“…Previous reports on such coordination include the interdependence of FA core compex stability and nuclear import (Garcia-Higuera et al, 2001;Pace et al, 2002;Leveille et al, 2006). We describe here an additional level of coordination at the level of transcription.…”

Section: Introductionmentioning

confidence: 78%

Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway

et al. 2008

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Fanconi anemia (FA) is a genome instability syndrome that is characterized by progressive bone marrow failure and a high risk of cancer. FA patients are particularly susceptible to leukemia as well as squamous cell carcinomas (SCCs) of the head and neck, anogenital region and skin. Thirteen complementation groups and the corresponding FA genes have been identified, and their protein products assemble into nuclear core complexes during DNA-damage responses. Much progress has been made in our understanding of post-translational FA protein modifications and physical interactions. By contrast, little is known about the control of protein availability at the level of transcription. We report here that multiple FA proteins were downregulated during the proliferative arrest of primary human keratinocytes and HeLa cells, and that the observed regulation was at a transcriptional level. Proliferative stimuli such as expression of HPV16 E7 as well as E2F1 overexpression in primary cells resulted in coordinate FA upregulation. To define the underlying mechanism, we examined the endogenous FANCD2 promoter, and detected regulated binding of members of the E2F/Rb family in chromatin immunoprecipitation assays. Finally, a 1 kb promoter fragment was sufficient to confer E2F/Rb regulation in reporter assays. Taken together, our data demonstrate FA gene co-regulation in synchrony with the cell cycle and suggest that deregulated expression of individual FA genes-in addition to FA gene mutation-may promote FA-related human cancer.

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Section: Introductionmentioning

confidence: 78%

Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway

et al. 2008

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“…Absence of the FANCA protein shortens the halflife of the FANCG protein (Garcia-Higuera et al 2000). Molecular studies support interactions between FANCG and FANCF (Garcia-Higuera et al 2000), between FANCE and FANCC (Pace et al 2002;Taniguchi and D'Andrea 2002), and between FANCB and FANCL subunits (Meetei et al 2004). The FANCE protein is required for the efficient transport of the FANCC protein to the nucleus (Pace et al 2002;Taniguchi and D'Andrea 2002).…”

Section: The Structure Of the Fa Complexmentioning

confidence: 95%

“…Molecular studies support interactions between FANCG and FANCF (Garcia-Higuera et al 2000), between FANCE and FANCC (Pace et al 2002;Taniguchi and D'Andrea 2002), and between FANCB and FANCL subunits (Meetei et al 2004). The FANCE protein is required for the efficient transport of the FANCC protein to the nucleus (Pace et al 2002;Taniguchi and D'Andrea 2002). Interestingly, yeast two-hybrid studies have also indicated that the N terminus of FANCE interacts directly with FANCD2 (Gordon and Buchwald 2003), implying that complex 1 may associate with FANCD2 through FANCE, thereby facilitating FANCD2 monoubiquitination.…”

Section: The Structure Of the Fa Complexmentioning

confidence: 96%

The Fanconi Anemia/BRCA pathway: new faces in the crowd

Kennedy¹,

D’Andrea²

2005

Genes Dev.

359

344

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Over the past few years, study of the rare inherited chromosome instability disorder, Fanconi Anemia (FA), has uncovered a novel DNA damage response pathway. Through the cooperation of multiple proteins, this pathway regulates a complicated cellular response to DNA cross-linking agents and other genotoxic stresses. In this article we review recent data identifying new components of the FA pathway that implicate it in several aspects of the DNA damage response, including the direct processing of DNA, translesion synthesis, homologous recombination, and cell cycle regulation. We also discuss new findings that explain how the FA pathway is regulated through the processes of ubiquitination and deubiquitination. We then consider the clinical implications of our current understanding of the FA pathway, particularly in the development and treatment of malignancy in heterozygous carriers of FA mutations or in patients with sporadic cancers. We consider how recent studies of p53-mediated apoptosis and loss of p53 function in models of FA may help explain the clinical features of the disease and finally present a hypothesis to account for the specificity of the FA pathway in the response to DNA cross-links.

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“…BRCA1-deficient cells are associated with a loss of DNA damageinducible FANCD2 subnuclear foci and monoubiquitination of FANCD2 (52). Several lines of evidence suggested that FANCD2 might be a target of BRCA1 E3 ubiquitin ligase activity (53,54). However, none of these studies have shown that FANCD2 was a direct substrate of the BRCA1/BARD1 ubiquitin ligase.…”

Section: A Functional Link Between Brca1 and Fanconi Anemia Proteinsmentioning

confidence: 99%

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

Zhang

Powell

2005

Molecular Cancer Research

181

150

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The tumor suppressor gene BRCA1 was cloned in 1994 based on its linkage to early-onset breast and ovarian cancer. Although the BRCA1 protein has been implicated in multiple cellular functions, the precise mechanism that determines its tumor suppressor activity is not defined. Currently, the emerging picture is that BRCA1 plays an important role in maintaining genomic integrity by protecting cells from double-strand breaks (DSB) that arise during DNA replication or after DNA damage. The DSB repair pathways available in mammalian cells are homologous recombination and nonhomologous end-joining. BRCA1 function seems to be regulated by specific phosphorylations in response to DNA damage and we will focus this review on the roles played by BRCA1 in DNA repair and cell cycle checkpoints. Finally, we will explore the idea that tumor suppression by BRCA1 depends on its control of DNA DSB repair, resulting in the promotion of error-free and the inhibition of error-prone recombinational repair.

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FANCE: the link between Fanconi anaemia complex assembly and activity

Cited by 154 publications

References 30 publications

Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway

Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway

The Fanconi Anemia/BRCA pathway: new faces in the crowd

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

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