ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response

Xiaohua Wu, Velvizhi Ranganathan, David S. Weisman, Walter F. Heine, David N. Ciccone, Ted B. O'Neill, Kindra E. Crick, Kerry A. Pierce, William S. Lane, Gary Rathbun, David M. Livingston and David T. Weaver
Additional contact information
Xiaohua Wu: Dana Farber Cancer Institute
Velvizhi Ranganathan: Center for Blood Research
David S. Weisman: Center for Blood Research
Walter F. Heine: Center for Blood Research
David N. Ciccone: Center for Blood Research
Ted B. O'Neill: Center for Blood Research
Kindra E. Crick: Dana Farber Cancer Institute
Kerry A. Pierce: Harvard Microchemistry Facility, Harvard University
William S. Lane: Harvard Microchemistry Facility, Harvard University
Gary Rathbun: Center for Blood Research
David M. Livingston: Dana Farber Cancer Institute
David T. Weaver: Center for Blood Research

Nature, 2000, vol. 405, issue 6785, 477-482

Abstract: Abstract Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer1. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to γ-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by γ-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after γ-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.

Date: 2000
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35013089 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:405:y:2000:i:6785:d:10.1038_35013089

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35013089

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().