NDLI: High mobility group protein B1 enhances DNA repair and chromatin modification after DNA damage

Content Provider	PubMed Central
Author	Lange, Sabine S. Mitchell, David L. Vasquez, Karen M.
Abstract	High mobility group protein B1 (HMGB1) is a multifunctional protein with roles in chromatin structure, transcriptional regulation, V(D)J recombination, and inflammation. HMGB1 also binds to and bends damaged DNA, but the biological consequence of this interaction is not clearly understood. We have shown previously that HMGB1 binds cooperatively with nucleotide excision repair damage recognition proteins to triplex-directed psoralen DNA interstrand cross-links (ICLs). Thus, we hypothesized that HMGB1 modulates the repair of DNA damage in mammalian cells. We demonstrate here that mammalian cells lacking HMGB1 are hypersensitive to DNA damage induced by psoralen plus UVA irradiation (PUVA) or UVC radiation, showing less survival and increased mutagenesis. In addition, nucleotide excision repair efficiency is significantly decreased in the absence of HMGB1 as assessed by the repair and removal of UVC lesions from genomic DNA. We also explored the role of HMGB1 in chromatin remodeling upon DNA damage. Immunoblotting demonstrated that, in contrast to HMGB1 proficient cells, cells lacking HMGB1 showed no histone acetylation upon DNA damage. Additionally, purified HMGB1 protein enhanced chromatin formation in an in vitro chromatin assembly system. These results reveal a role for HMGB1 in the error-free repair of DNA lesions. Its absence leads to increased mutagenesis, decreased cell survival, and altered chromatin reorganization after DNA damage. Because strategies targeting HMGB1 are currently in development for treatment of sepsis and rheumatoid arthritis, our findings draw attention to potential adverse side effects of anti-HMGB1 therapy in patients with inflammatory diseases.
Related Links	http://dx.doi.org/10.1073/pnas.0803181105
Starting Page	10320
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	30
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-07-29
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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