The Fanconi anemia pathway and ubiquitin

Céline Jacquemont,Toshiyasu Taniguchi

doi:10.1186/1471-2091-8-s1-s10

Céline Jacquemont, Toshiyasu Taniguchi

Open Access

https://doi.org/10.1186/1471-2091-8-s1-s10

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Abstract

Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia, cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking agents, such as cisplatin. To date, 12 FA gene products have been identified, which cooperate in a common DNA damage-activated signaling pathway regulating DNA repair (the FA pathway). Eight FA proteins form a nuclear complex harboring E3 ubiquitin ligase activity (the FA core complex) that, in response to DNA damage, mediates the monoubiquitylation of the FA protein FANCD2. Monoubiquitylated FANCD2 colocalizes in nuclear foci with proteins involved in DNA repair, including BRCA1, FANCD1/BRCA2, FANCN/PALB2 and RAD51. All these factors are required for cellular resistance to DNA crosslinking agents. The inactivation of the FA pathway has also been observed in a wide variety of human cancers and is implicated in the sensitivity of cancer cells to DNA crosslinking agents. Drugs that inhibit the FA pathway may be useful chemosensitizers in the treatment of cancer.Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; ).

Highlights

Fanconi anemia Fanconi anemia (FA) is a rare autosomal or X-linked recessive disease characterized by chromosomal instability and cancer susceptibility
FANCD2, FANCD1/BRCA2, FANCN/PALB2 and BRCA1 colocalize in nuclear foci at the site of DNA damage [32][34,35] and BRCA1 itself is required for efficient nuclear foci formation of FANCD2 [34,36]
Even though a direct DNA binding activity has been demonstrated for unmodified FANCD2 in vitro[43], monoubiquitylation of the protein is required for its translocation to chromatin in vivo and nuclear foci formation at the site of DNA damage, as well as for cellular resistance to DNA crosslinking agents [34,44]

Summary

Introduction

Fanconi anemia Fanconi anemia (FA) is a rare autosomal or X-linked recessive disease characterized by chromosomal instability and cancer susceptibility. The FA core complex and monoubiquitylation of FANCD2 Ubiquitin plays a crucial role in the regulation of the FA pathway.

Results

Conclusion