ATR Couples FANCD2 Monoubiquitination to the DNA-damage Response

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Aug 18

PMID 15314022

Citations 194

Authors

Paul R Andreassen

Alan D DAndrea

Toshiyasu Taniguchi

Affiliations

Soon will be listed here.

Abstract

Fanconi anemia (FA) is a multigenic autosomal recessive cancer susceptibility syndrome. The FA pathway regulates the monoubiquitination of FANCD2 and the assembly of damage-associated FANCD2 nuclear foci. How FANCD2 monoubiquitination is coupled to the DNA-damage response has remained undetermined. Here, we demonstrate that the ATR checkpoint kinase and RPA1 are required for efficient FANCD2 monoubiquitination. Deficiency of ATR function, either in Seckel syndrome, which clinically resembles Fanconi anemia, or by siRNA silencing, results in the formation of radial chromosomes in response to the DNA cross-linker, mitomycin C (MMC), thus mimicking the chromosome instability of FA cells.

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