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PMID: 15314022 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

ATR couples FANCD2 monoubiquitination to the DNA-damage response.

Genes & development ·Vol. 18 ·No. 16 ·2004-08-15 ·Pages 1958-63

Andreassen PR, D'Andrea AD, Taniguchi T

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.

MeSH Terms
Ataxia Telangiectasia Mutated Proteins Base Sequence Cell Cycle Proteins/metabolism Cell Line DNA Damage DNA Primers DNA Repair Fanconi Anemia Complementation Group D2 Protein Flow Cytometry Humans Microscopy, Fluorescence Nuclear Proteins/metabolism Protein Serine-Threonine Kinases/metabolism Ubiquitin/metabolism
Chemicals
Cell Cycle Proteins DNA Primers FANCD2 protein, human Fanconi Anemia Complementation Group D2 Protein Nuclear Proteins Ubiquitin ATR protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Andreassen Paul R
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
D'Andrea Alan D
Taniguchi Toshiyasu
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1196104
Published
2004-08-15
Pages
1958-63
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC514175
Subset
IM
Grants
NHLBI NIH HHS · R01 HL052725 · United States
NHLBI NIH HHS · P01HL54785 · United States
NHLBI NIH HHS · P50 HL054785 · United States
NHLBI NIH HHS · R01HL52725 · United States
NIDDK NIH HHS · R01 DK043889 · United States
NIDDK NIH HHS · R01DK43889 · United States
External Links
PubMed source DOI: 10.1101/gad.1196104 PMC Full Text View journal details
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