Revisiting the role of heterochromatin protein 1 in DNA repair

Abstract

Heterochromatin protein 1 (HP1) is a conserved factor critical for heterochromatin organization and gene silencing. It is recruited to chromatin by its direct interaction with H3K9me (methylated lysine 9 residue of histone H3), an epigenetic mark for silenced chromatin. Now, Luijsterburg et al. (Luijsterburg, M.S., C. Dinant, H. Lans, J. Stap, E. Wiernasz, S. Lagerwerf, D.O. Warmerdam, M. Lindh, M.C. Brink, J.W. Dobrucki, et al. 2009. J. Cell Biol. 185:577-586) reveal a new H3K9me-independent role for HP1 in the DNA damage response, which is distinct from the one recently reported by Ayoub et al. (Ayoub, N., A.D. Jeyasekharan, J.A. Bernal, and A.R. Venkitaraman. 2008. Nature. 453:682-686).

Figure 1.

HP1 and DNA repair. (A) A schematic diagram of HP1. The CD binds to H3K9me, whereas the CSD is involved in dimerization and multiple protein interactions (for reviews see Lomberk et al., 2006; Fanti and Pimpinelli, 2008). T51 is phosphorylated by CK2 in response to DNA damage, which reduces the affinity of HP1 for H3K9me (Ayoub et al., 2008). The CSD, but not the CD, is required for DNA damage site targeting (Luijsterburg et al., 2009). P, phosphorylation. (B) Summary of HP1 behaviors at the damage sites according to Ayoub et al. (2008) and Luijsterburg et al. (2009). According to the observation made by Ayoub et al. (2008), HP1 transiently dissociates from H3K9me in response to damage. In contrast, Luijsterburg et al. (2009) found that HP1 is actively recruited to DNA damage sites in an H3K9me-independent manner.