• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function.

Previous work has shown several proteins defective in Fanconi anemia (FA) are phosphorylated in a functionally critical manner. FANCA is phosphorylated after DNA damage and localized to chromatin, but the site and significance of this phosphorylation are unknown. Mass spectrometry of FANCA revealed one phosphopeptide, phosphorylated on serine 1449. Serine 1449 phosphorylation was induced after DNA damage but not during S phase, in contrast to other posttranslational modifications of FA proteins. Furthermore, the S1449A mutant failed to completely correct a variety of FA-associated phenotypes. The DNA damage response is coordinated by phosphorylation events initiated by apical kinases ATM (ataxia telangectasia mutated) and ATR (ATM and Rad3-related), and ATR is essential for proper FA pathway function. Serine 1449 is in a consensus ATM/ATR site, phosphorylation in vivo is dependent on ATR, and ATR phosphorylated FANCA on serine 1449 in vitro. Phosphorylation of FANCA on serine 1449 is a DNA damage-specific event that is downstream of ATR and is functionally important in the FA pathway.

Pubmed ID: 19109555

Authors

  • Collins NB
  • Wilson JB
  • Bush T
  • Thomashevski A
  • Roberts KJ
  • Jones NJ
  • Kupfer GM

Journal

Blood

Publication Data

March 5, 2009

Associated Grants

  • Agency: PHS HHS, Id: R01-063776

Mesh Terms

  • Alkylating Agents
  • Ataxia Telangiectasia Mutated Proteins
  • Blotting, Western
  • Cell Cycle Proteins
  • DNA Damage
  • Electrophoresis, Polyacrylamide Gel
  • Fanconi Anemia
  • Fanconi Anemia Complementation Group A Protein
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Mitomycin
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Serine