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			PubMed Journals: Nat Cell Biol

  Source:		PMID: 12447395


    		Nat Cell Biol. 2002 Dec;4(12):913-20.
     
			Interaction of FANCD2 and NBS1 in the DNA
			damage response.

			Nakanishi K(1), Taniguchi T, Ranganathan
			V, New HV, Moreau LA, Stotsky M, Mathew
			CG, Kastan MB, Weaver DT, D'Andrea AD.

			Author Information
			(1) Department of Pediatric Oncology,
			Dana-Farber Cancer Institute, 44 Binney
			Street, Boston, MA 02115, USA.

			Fanconi anaemia (FA) and Nijmegen breakage
			syndrome (NBS) are autosomal recessive chromosome
			instability syndromes with distinct clinical
			phenotypes. Cells from individuals affected
			with FA are hypersensitive to mitomycin
			C (MMC), and cells from those with NBS are
			hypersensitive to ionizing radiation. Here
			we report that both NBS cell lines and individuals
			with NBS are hypersensitive to MMC, indicating
			that there may be functional linkage between
			FA and NBS. In wild-type cells, MMC activates
			the colocalization of the FA subtype D2
			protein (FANCD2) and NBS1 protein in subnuclear
			foci. Ionizing radiation activates the ataxia
			telangiectasia kinase (ATM)-dependent and NBS1-dependent
			phosphorylation of FANCD2, resulting in
			an S-phase checkpoint. NBS1 and FANCD2 therefore
			cooperate in two distinct cellular functions,
			one involved in the DNA crosslink response
			and one involved in the S-phase checkpoint
			response.

			DOI: 10.1038/ncb879 PMID: 12447395 [Indexed
			for MEDLINE]

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