title: Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin.
abstract: We report that HMGN1, a nucleosome binding protein that destabilizes the higher-order chromatin structure, modulates the repair rate of ultraviolet light (UV)-induced DNA lesions in chromatin. Hmgn1(-/-) mouse embryonic fibroblasts (MEFs) are hypersensitive to UV, and the removal rate of photoproducts from the chromatin of Hmgn1(-/-) MEFs is decreased as compared with the chromatin of Hmgn1(+/+) MEFs; yet, host cell reactivation assays and DNA array analysis indicate that the nucleotide excision repair (NER) pathway in the Hmgn1(-/-) MEFs remains intact. The UV hypersensitivity of Hmgn1(-/-) MEFs could be rescued by transfection with plasmids expressing wild-type HMGN1 protein, but not with plasmids expressing HMGN1 mutants that do not bind to nucleosomes or do not unfold chromatin. Transcriptionally active genes, the main target of the NER pathways in mice, contain HMGN1 protein, and loss of HMGN1 protein reduces the accessibility of transcribed genes to nucleases. By reducing the compaction of the higher-order chromatin structure, HMGN1 facilitates access to UV-damaged DNA sites and enhances the rate of DNA repair in chromatin.
authors.affiliation: Protein Section, LM, Basic Research Laboratory, CCR, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Birger
authors.forename: Katherine L
authors.initials: KL
authors.lastname: West
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Postnikov
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Lim
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.forename: James P
authors.initials: JP
authors.lastname: Wagner
authors.forename: Craig S
authors.initials: CS
authors.lastname: Laufer
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D024241:HMGN1 Protein / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011233:Precipitin Tests; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D002843:Chromatin; D024241:HMGN1 Protein