Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways.

Published

Journal Article

Fanconi anemia (FA) and ataxia telangiectasia (AT) are clinically distinct autosomal recessive disorders characterized by spontaneous chromosome breakage and hematological cancers. FA cells are hypersensitive to mitomycin C (MMC), while AT cells are hypersensitive to ionizing radiation (IR). Here, we identify the Fanconi anemia protein, FANCD2, as a link between the FA and ATM damage response pathways. ATM phosphorylates FANCD2 on serine 222 in vitro. This site is also phosphorylated in vivo in an ATM-dependent manner following IR. Phosphorylation of FANCD2 is required for activation of an S phase checkpoint. The ATM-dependent phosphorylation of FANCD2 on S222 and the FA pathway-dependent monoubiquitination of FANCD2 on K561 are independent posttranslational modifications regulating discrete cellular signaling pathways. Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity.

Full Text

Duke Authors

Cited Authors

  • Taniguchi, T; Garcia-Higuera, I; Xu, B; Andreassen, PR; Gregory, RC; Kim, S-T; Lane, WS; Kastan, MB; D'Andrea, AD

Published Date

  • May 2002

Published In

Volume / Issue

  • 109 / 4

Start / End Page

  • 459 - 472

PubMed ID

  • 12086603

Pubmed Central ID

  • 12086603

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(02)00747-x

Language

  • eng