Rif1, a Conserved Chromatin Factor Regulating DNA Replication, DNA Repair, and Transcription

Rif1, originally discovered as a telomere binding factor in yeast, is evolutionally conserved and regulates various aspects of chromosome reactions including repair, DNA replication, and transcription in addition to telomere regulation. In mammals, Rif1 suppresses homologous recombination-dependent repair and stimulates non-homologous end-joining repair of double-stranded DNA breaks. Rif1 plays a crucial role in regulating timing of genome replication during S phase. It also affects the transcription profiles. Rif1, composed of the N-terminal HEAT repeat domain and the C-terminal DNA binding/oligomerization domain, tightly binds to chromatin and may facilitate the formation of chromatin domains that may be repressive for initiation of replication as well as for transcription. Rif1 also binds to many factors including protein phosphatase 1, which plays a role in suppression of origin firing. Rif1 is expressed at a high level in mouse embryonic stem (ES) cells and is involved in regulation of differentiation processes.