![]() These cells were analyzed by live cell microscopy to monitor the amount of time needed for full mitotic progression from nuclear envelope breakdown (NEB) until the separation of the sister chromatids in anaphase (Fig. To enhance our insight into the role of SUMOylation 24– 26 specifically during mitosis, we have produced HeLa cell lines stably harboring inducible knockdown constructs for both subunits of the SUMO-activating enzyme (SAE1 and SAE2). Inhibition of SUMOylation leads to mitotic delay This work represents a prime example of how SUMO and ubiquitin cooperate to drive mitosis. SUMOylation enhances the activity of the APC/C to a subset of its targets. Searching for relevant SUMOylated proteins in mitosis, we identify the APC/C as a SUMO-regulated target. Here we show that disrupting SUMO signal transduction results in a delay in mitosis and causes defects in mitotic chromosome separation. We are still limited in our understanding of the target proteins regulated by SUMO during cell cycle progression 25. Mice lacking UBC9 die at an early post-implantation stage, showing defective chromosome segregation, resulting in anaphase bridges 24. Intriguingly, disruption of the UBC9 gene in yeast was found to block cell cycle progression, leading to a block in G2 phase or in early mitosis 23. SUMO conjugation is regulated by a single E2, UbE2I, previously known as UBC9 22. SUMOs are predominantly conjugated to nuclear proteins and regulate all nuclear processes 20, 21. NEDD8 is a key activator of Cullin-like RING ligases, by modifying a conserved lysine in the Cullin subunits 19. In addition to ubiquitin, ubiquitin family members NEDD8 and small ubiquitin-like modifier (SUMO) also contribute to proper cell cycle progression. Therefore, activity of the APC/C is tightly controlled by binding of inhibitors and activators, destabilization of its subunits, and PTMs, such as phosphorylation 10– 13.ĭeregulation of these control mechanisms and altered activity of the APC/C can therefore lead to severe mitotic defects and genome instabilities and has been associated with the development of various human cancer types 14– 18. ![]() The timely destruction of these regulators is essential for an error-free chromosomal segregation and successful cell division. Securin is the inhibitor of the Cohesion cleaving protein Separase. The APC/C initiates mitotic exit and governs the progression to G1 phase by targeting key regulators, such as Cyclin B and Securin, for proteasomal degradation 10. Two different ubiquitin E2s aid the APC/C to ubiquitylate its substrates, UBE2C and UBE2S 9. The APC/C is a 1.2 MDa complex, comprised of 15 subunits, including structural parts like APC1, APC4, and APC5, catalytic components, and the two substrate adapters known as co-activators CDH1 and CDC20 8. The abundance of critical cell cycle components is regulated by the ubiquitin–proteasome system, with a dominant role for the ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) 7, 8. Kinases play a particularly well-known role in cell cycle progression. The complexity of these PTMs at the proteome-wide scale is overwhelming 6. We are limited in our understanding of the intricate interplay between different PTMs. Enzymes that mediate the conjugation and de-conjugation of PTMs are key drug targets 5. Cell cycle progression is exquisitely regulated by protein posttranslational modifications (PTMs) including phosphorylation and ubiquitylation 4. Unrepaired DNA damage and unbalanced separation of chromosome pairs in mitosis lead to loss of genomic integrity including aneuploidy and can potentially lead to pathology including cancer 1– 3. Don't let this confuse you into turning to the side.Faithful copying of the genetic information and accurate separation of chromosomes during mitosis are essential to maintain genomic integrity. The white blob will get really large when you get close to the other robot. The white blob might be small if the other robot is on the other side of the ring, or only partially in view. ![]() This is an example of "servoing on a target". So maybe it would be better to control the left and right wheels simultaneously to change the robot's direction. Meanwhile the other robot might have moved. However, your idea of rotating first then driving means that you must what a little while for the rotation to complete. Even your own motion will change where it appears in the image. Your opponent is not standing still, so you need to keep updating your direction. If you cannot see a white blob, it is probably because the opponent is behind you. If you find what is sometimes called the center of gravity of the blob and target that you should head in the right direction. What you probably want to do is detect a white blob, i.e. Have a look in the Technologies\Vision folder. There are sample vision services included in RDS. However, you will have to do it using the webcam.
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