We demonstrate here that specific mutations within the RFTS domain of Raf2 result in the loss of the classic marks of heterochromatin, namely H3K9 methylation and Swi6, but maintain siRNA production. Thus, as previously documented for specific mutations within Raf1 and Cul4, mutation in the RFTS domain of Raf2 uncouple chromatin modification from siRNA production. This effect may be due to partial disruption of the CLRC; the point mutants studied may be able to maintain specific interactions required for siRNA generation but lose those that are critical for H3K9 methylation and subsequent protein associations. It may be that, as seen in specific Raf1 mutants, siRNA levels remain high because the defective Raf2 RFTS mutations inhibit the degradation of pre-existing siRNAs. Another tenable explanation is that the particular Raf2 RFTS mutants analysed do not disrupt the continual synthesis of siRNAs from centromere repeat transcripts. In fact, since Raf2 has been shown to interact with Cdc20, this could provide a molecular link between DNA replication, siRNA production and chromatin modification. More extensive analyses of such interactions in cells harboring mutations such as those in the Raf2 RFTS mutation should provide insight into the interplay between Raf2, Cdc20 and the role of DNA replication in these processes and allow further dissection of the role of the CLRC complex in RNAidirected heterochromatin formation. Stroke is one of the major causes of death and adult disability. The risk of stroke KS176 dramatically increases along aging and three quarters of all strokes occur in people over the age of 65. Type 2 diabetes increases the risk of stroke 2-6-fold when compared with non-diabetic individuals. In addition, T2D doubles the risk of stroke GSK-J4 recurrence and increases mortality. Neuroprotective strategies aimed at decreasing brain damage after stroke have failed to be translated into the clinical setting along the past decades. Today, tissue plasminogen activator is the only established pharmacological treatment that restores brain reperfusion. However, only a low rate of patients receives tPA due to delayed hospitalization and side effects.