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.