The Emerging Role of HP1 in the DNA Damage Response

Abstract

Heterochromatin protein 1 (HP1) family members are versatile proteins involved in transcription, chromatin organization, and replication. Recent findings now have 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 also was proposed based on the finding that all HP1 isoforms are recruited to UV-induced lesions, oxidative lesions, and DNA breaks. The loss of HP1 renders nematodes highly sensitive to DNA damage, and mice lacking HP1beta suffer from genomic instability, suggesting that the loss of HP1 is not necessarily beneficial for repair. These findings raise the possibility that HP1 facilitates DNA repair by reorganizing 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.