Small ubiquitin-like modifier (SUMO1-3) constitutes a group of proteins that 
conjugate to lysine residues of target proteins thereby modifying their 
activity, stability, and subcellular localization. A large number of SUMO target 
proteins are transcription factors and other nuclear proteins involved in gene 
expression. Furthermore, SUMO conjugation plays key roles in genome stability, 
quality control of newly synthesized proteins, proteasomal degradation of 
proteins, and DNA damage repair. Any marked increase in levels of 
SUMO-conjugated proteins is therefore expected to have a major impact on the 
fate of cells. We show here that SUMO conjugation is activated in human 
astrocytic brain tumors. Levels of both SUMO1- and SUMO2/3-conjugated proteins 
were markedly increased in tumor samples. The effect was least pronounced in 
low-grade astrocytoma (WHO Grade II) and most pronounced in glioblastoma 
multiforme (WHO Grade IV). We also found a marked rise in levels of Ubc9, the 
only SUMO conjugation enzyme identified so far. Blocking SUMO1-3 conjugation in 
glioblastoma cells by silencing their expression blocked DNA synthesis, cell 
growth, and clonogenic survival of cells. It also resulted in DNA-dependent 
protein kinase-induced phosphorylation of H2AX, indicative of DNA double-strand 
damage, and G(2) /M cell cycle arrest. Collectively, these findings highlight 
the pivotal role of SUMO conjugation in DNA damage repair processes and imply 
that the SUMO conjugation pathway could be a new target of therapeutic 
intervention aimed at increasing the sensitivity of glioblastomas to 
radiotherapy and chemotherapy.