Role of SUMO/Ubc9 in DNA damage repair and tumorigenesis.
DNA damage repair is an important cell function for genome integrity and its deregulation can lead to genomic instability and development of malignancies. Sumoylation is an increasingly important ubiquitin-like modification of proteins affecting protein stability, enzymatic activity, nucleocytoplasmic trafficking, and protein-protein interactions. In particular, several important DNA repair enzymes are subject to sumoylation, which appears to play a role in copping with DNA damage insults. Recent reports indicate that Ubc9, the single SUMO E2 enzyme catalyzing the conjugation of SUMO to target proteins, is overexpressed in certain tumors, such as lung adenocarcinoma, ovarian carcinoma and melanoma, suggestive of its clinic significance. This review summarizes the most important DNA damage repair pathways which are potentially affected by Ubc9/SUMO and their role in regulating the function of several proteins involved in the DNA damage repair machinery.
Moschos
Stergios J
SJ
Department of Medicine, Division of Hematology-Oncology, Hillman Cancer Research Pavilion, University of Pittsburgh Medical Center, 5117 Centre Avenue, Suite 1.32e, Pittsburgh, PA 15213, USA.
Mo
Yin-Yuan
YY
D002843:Chromatin / Q000737:chemistry; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D002843:Chromatin; D004798:Enzymes; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D051135:Rad51 Recombinase; D004265:DNA Helicases; D000098843:Ubiquitin-Conjugating Enzyme UBC9