The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage

Zhiwan Dong, Qing Zhong, Phang Lang Chen

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The Nijmegen breakage syndrome (NBS), a chromosomal instability disorder, is characterized in part by cellular hypersensitivity to ionizing radiation. Repair of DNA double-strand breaks by radiation is dependent on a multifunctional complex containing Rad50, Mre11, and the NBS1 gene product, p95 (NBS protein, nibrin). The role of p95 in these repair processes is unknown. Here it is demonstrated that Mre11 is hyperphosphorylated in a cell cycle-independent manner in response to treatment of cells with genotoxic agents including γ irradiation. This response is abrogated in two independently established NBS cell lines that have undetectable levels of the p95 protein. NBS cells are also deficient for radiation-induced nuclear foci containing Mre11, while those with Rad51 are unaffected. An analysis of the kinetic relationship between Mre11 phosphorylation and the appearance of its radiation-induced foci indicates that the former precedes the latter. Together, these data suggest that specific phosphorylation of Mre11 is induced by DNA damage, and p95 is essential in this process, perhaps by recruiting specific kinases.

Original languageEnglish (US)
Pages (from-to)19513-19516
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number28
DOIs
StatePublished - Jul 9 1999

Fingerprint

Nijmegen Breakage Syndrome
Phosphorylation
DNA Damage
Cells
Radiation
DNA
Repair
Proteins
Ionizing radiation
Chromosome Disorders
Chromosomal Instability
Double-Stranded DNA Breaks
Phosphotransferases
Genes
Ionizing Radiation
Irradiation
Cell Cycle
Hypersensitivity
Kinetics
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. / Dong, Zhiwan; Zhong, Qing; Chen, Phang Lang.

In: Journal of Biological Chemistry, Vol. 274, No. 28, 09.07.1999, p. 19513-19516.

Research output: Contribution to journalArticle

Dong, Zhiwan ; Zhong, Qing ; Chen, Phang Lang. / The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 28. pp. 19513-19516.
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