Taken together, the reduced capacity of the tethered eIF4GI core domain to suppress NMD in the eIF3f and eIF3h knockdowns and the association between the eIF4GI core domain and eIF3 identify the eIF4G-eIF3 connection as part of a new NMD antagonizing pathway that is genetically separable from the previously described PABPC1-mediated NMD inhibition. That tethering of individual eIF3 subunits failed to inhibit NMD could simply be due to the inability of these MS2 fusion proteins to assemble functional eIF3 complexes. The loss of Suv39h1 and Suv39h2 Sulfamethazine HMTases in mouse model abolished H3K9 methylation at pericentric heterochromatin and induced chromosomal instability. However, single gene disruptions for either Suv39h1 or Suv39h2 did not appear to affect viability and fertility of mutant mice, suggesting these two enzymes are redundant. Study in G9a knockout mouse showed that G9a was necessary for embryonic development or differentiation and embryonic growth defect in G9a-deficient ES cells might be due to apoptotic cell death but not cell cycle arrest. In that model, chromosomal instability was not perceived in the knockout cells. We found here that in cancer cells, which often harbor aberrant numbers of chromosome, G9a KD induced centrosome disruption and more extensive chromosome instability, which resulted in inhibition of cell growth and cellular senescence. It SRPIN340 appeared that 3MeH3K9 was also diminished at euchromatic region in the G9a KD cells. This might be due to the drastic decreasing of 2MeH3K9, which is prerequisite for modification of tri-methylation on the loci. These data suggested that the role of G9a in cancer cells is critical and appears to be protecting further chromosomal disruption. By contrast, single Suv39H1 KD partially abolished 3MeH3K9 at pericentric region but could not induce chromosomal instability, probably due to redundant roles for SUV39H HMTases.Recent reports demonstrated that centromeric chromatin specific combinations of histone modifications and the three dimensional organization of chromosomes could also be important for recruitment of cohesion complexes to heterochromatin near sister kinetochores.