TAILIEUCHUNG - Báo cáo khoa học: The nucleosome-binding protein HMGN2 modulates global genome repair

The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here, we report that DT40 chicken cells lacking eitherHMGN2orHMGN1a, or lacking both HMGN1aand HMGN2, are hypersensitive to killing by UV irradiation. Loss of both HMGN1aand HMGN2or only HMGN2increases the extent of UV-induced G2 –M checkpoint arrest and the rate of apoptosis. | The nucleosome-binding protein HMGN2 modulates global genome repair Mangalam Subramanian1 Rhiannon W. Gonzalez1 Hemangi Patil1 Takahiro Ueda2 Jae-Hwan Lim3 f Kenneth H. Kraemer2 Michael Bustin3 and Michael Bergel1 3 1 Department of Biology Texas Woman s University Denton TX USA 2 Basic Research Laboratory Center for Cancer Research NationalCancer Institute NationalInstitutes of Health Bethesda MD USA 3 Protein Section Laboratory of Metabolism NationalCancer Institute NationalInstitutes of Health Bethesda MD USA Keywords apoptosis cell cycle chromatin DNA repair UV irradiation Correspondence M. Bergel Department of Biology Texas Woman s University PO Box 425799 Denton TX 76204-5799 USA Fax 1 940 898 2382 Tel 1 940 898 2471 E-mail MBergel@ Present address Pharmaceuticals and MedicalDevices Agency Tokyo Japan fDepartment of BiologicalScience Andong NationalUniversity Andong 760-749 Korea The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here we report that DT40 chicken cells lacking either HMGN2 or HMGNla or lacking both HMGNla and HMGN2 are hypersensitive to killing by UV irradiation. Loss of both HMGNla and HMGN2 or only HMGN2 increases the extent of UV-induced G2-M checkpoint arrest and the rate of apoptosis. HMGN null mutant cells showed slower removal of UV-induced DNA lesions from native chromatin but the nucleotide excision repair remained intact as measured by host cell reactivation assays. These results identify HMGN2 as a component of the global genome repair subpathway of the nucleotide excision repair pathway and may indicate that HMGN2 facilitates the ability of the DNA repair proteins to access and repair UV-induced DNA lesions in chromatin. Our finding that HMGNs play a role in global DNA repair expands the role of these proteins in the maintenance of genome integrity. Received 12 April 2009 revised 17 August 2009 accepted 14 September 2009 doi .

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