PubMed Journals: Nature

  Source:		PMID: 10839544

    		Nature. 2000 May 25;405(6785):473-7.
			Functional link between ataxia-telangiectasia and Nijmegen
			breakage syndrome gene products.

			Zhao S(1), Weng YC, Yuan SS, Lin YT, Hsu
			HC, Lin SC, Gerbino E, Song MH, Zdzienicka
			MZ, Gatti RA, Shay JW, Ziv Y, Shiloh Y,
			Lee EY.

			Author Information
			(1) Department of Molecular Medicine/Institute
			of Biotechnology,
			The University of Texas Health Science Center at San Antonio,
			78245-3207, USA.

			Comment in Nature. 2000 May 25;405(6785):404-5.

			Ataxia-telangiectasia (A-T) and Nijmegen
			breakage syndrome (NBS) are recessive genetic
			disorders with susceptibility to cancer
			and similar cellular phenotypes. The protein
			product of the gene responsible for A-T,
			designated ATM, is a member of a family
			of kinases characterized by a carboxy-terminal
			phosphatidylinositol 3-kinase-like domain.
			The NBS1 protein is specifically mutated
			in patients with Nijmegen breakage syndrome
			and forms a complex with the DNA repair
			proteins Rad50 and Mrel1. Here we show that
			phosphorylation of NBS1, induced by ionizing
			radiation, requires catalytically active
			ATM. Complexes containing ATM and NBS1 exist
			in vivo in both untreated cells and cells
			treated with ionizing radiation. We have
			identified two residues of NBS1, Ser 278
			and Ser 343 that are phosphorylated in vitro
			by ATM and whose modification in vivo is
			essential for the cellular response to DNA
			damage. This response includes S-phase checkpoint
			activation, formation of the NBS1/Mrel1/Rad50
			nuclear foci and rescue of hypersensitivity
			to ionizing radiation. Together, these results
			demonstrate a biochemical link between cell-cycle
			checkpoints activated by DNA damage and
			DNA repair in two genetic diseases with
			overlapping phenotypes.

			DOI: 10.1038/35013083 PMID: 10839544 [Indexed
			for MEDLINE]

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