MCB Accepts, published online ahead of print on 5 October 2009

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Mol. Cell. Biol. doi:10.1128/MCB.01048-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Emerging Role of HP1 in the DNA Damage Response

Christoffel Dinant^* and Martijn S. Luijsterburg^*

Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark; Department of Cell and Molecular Biology (CMB), Karolinska Institutet, von Eulers väg 3, S-17177 Stockholm, Sweden

^* To whom correspondence should be addressed. Email: cdi{at}cancer.dk. martijn.luijsterburg{at}ki.se.

Heterochromatin protein 1 (HP1) family members are versatile proteins involved in transcription, chromatin organization and replication. Recent findings have now implicated HP1 proteins in the DNA damage response as well. Cell-biological approaches showed that reducing the levels of all three HP1 isoforms enhances DNA repair, possibly due to heterochromatin relaxation. Additionally, HP1 is phosphorylated in response to DNA damage, which was suggested to initiate the DNA damage response. These findings have led to the conclusion that heterochromatic proteins are inhibitory to repair and that their dissociation from heterochromatin may facilitate repair. In contrast with an inhibitory role, a more active role for HP1 in DNA repair was also proposed based on the finding that all HP1 isoforms are recruited to UV-induced lesions, oxidative lesions and DNA breaks. Loss of HP1 renders nematodes highly sensitive to DNA damage and mice lacking HP1 suffer from genomic instability, suggesting that loss of HP1 is not necessarily beneficial for repair. These findings raise the possibility that HP1 may facilitate DNA repair by re-organizing chromatin, which may involve interactions between phosphorylated HP1 and other DNA damage response proteins. Taken together, these studies illustrate an emerging role of HP1 proteins in the response to genotoxic stress.