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More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance

Abstract

Following the discovery in 1998 of γ-H2AX, the first histone modification induced by DNA damage1, interest in the changes to chromatin induced by DNA damage has exploded, and a vast amount of information has been generated. However, there has been a discrepancy between our rapidly advancing knowledge of how chromatin responds to DNA damage and the understanding of why cells mobilize large segments of chromatin to protect the genome against destabilizing effects posed by tiny DNA lesions. Recent research has provided insights into these issues and suggests that chromatin responses induced by DNA damage are not simply the accumulation of 'nuclear foci' but are mechanisms required to guard genome integrity.

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Figure 1: Chromatin responses to DNA damage are orchestrated by a series of post-translational modifications.
Figure 2: Post-translational modifications that affect chromatin organization and recruit additional genome caretakers to promote repair and suppress transcription in the vicinity of DNA lesions.
Figure 3: Chromatin domains formed in G1 nuclei and enriched in 53BP1 protect DNA lesions generated by mitotic passage of under-replicated chromosomes.
Figure 4: Chromatin modifications restrain unscheduled resection of DNA ends.

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Acknowledgements

The authors wish to thank the Danish Cancer Society, the Danish National Research Foundation, the Danish Research Council, the John and Birthe Meyer Foundation, and the European Commission (DDResponse, Biomedreg) for financial support. Special thanks go to M. Altmeyer, C. Dinant, V. Savic, and L. Toledo for comments on the manuscript.

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Lukas, J., Lukas, C. & Bartek, J. More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13, 1161–1169 (2011). https://doi.org/10.1038/ncb2344

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