Showing papers by "Angelika Amon published in 2009"

The rate of cell growth is governed by cell cycle stage

Abstract: Cell growth is an essential requirement for cell cycle progression. While it is often held that growth is independent of cell cycle position, this relationship has not been closely scrutinized. Here we show that in budding yeast, the ability of cells to grow changes during the cell cycle. We find that cell growth is faster in cells arrested in anaphase and G1 than in other cell cycle stages. We demonstrate that the establishment of a polarized actin cytoskeleton—either as a consequence of normal cell division or through activation of the mating pheromone response—potently attenuates protein synthesis and growth. We furthermore show by population and single-cell analysis that growth varies during an unperturbed cell cycle, slowing at the time of polarized growth. Our study uncovers a fundamental relationship whereby cell cycle position regulates growth.

Aneuploidy: cancer's fatal flaw?

Abstract: Aneuploidy is a characteristic of cancer, with greater than 90 percent of all solid tumors in humans carrying an aberrant karyotype. Yet whether and how this condition contributes to tumorigenesis is not understood. Here we summarize our recent findings on the effects of aneuploidy on cell physiology and proliferation. These studies suggest that aneuploidy puts significant stress on the cell, which responds to this condition in what can be viewed as an aneuploidy stress response. We will discuss how our results may bear on our understanding of the role of this condition in tumorigenesis and how they may provide new opportunities for treatment of the disease.

The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4.

Abstract: In budding yeast, a surveillance mechanism known as the spindle position checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle misposition, the checkpoint delays exit from mitosis by restraining the activity of the mitotic exit network (MEN). To date, the only component of the checkpoint to be identified is the protein kinase Kin4. Furthermore, how the kinase is regulated by spindle position is not known. Here, we identify the protein phosphatase 2A (PP2A) in complex with the regulatory subunit Rts1 as a component of the SPOC. Loss of PP2A-Rts1 function abrogates the SPOC but not other mitotic checkpoints. We further show that the protein phosphatase functions upstream of Kin4, regulating the kinase's phosphorylation and localization during an unperturbed cell cycle and during SPOC activation, thus defining the phosphatase as a key regulator of SPOC function.

Regulation of Spo12 Phosphorylation and Its Essential Role in the FEAR Network

Abstract: Summary Background In budding yeast, the protein phosphatase Cdc14 coordinates late mitotic events and triggers exit from mitosis. During early anaphase, Cdc14 is activated by the FEAR network, but how signaling through the FEAR network occurs is poorly understood. Results We find that the FEAR network component Spo12 is phosphorylated on S118. This phosphorylation is essential for Spo12 function and is restricted to early anaphase, when the FEAR network is active. The anaphase-specific phosphorylation of Spo12 requires mitotic CDKs and depends on the FEAR network components Separase and Slk19. Furthermore, we find that CDC14 is required to maintain Spo12 in the dephosphorylated state prior to anaphase. Conclusions Our results show that anaphase-specific phosphorylation of Spo12 is essential for FEAR network function and raise the interesting possibility that Cdc14 itself helps to prevent the FEAR network from being prematurely activated.

Effects of Age on Meiosis in Budding Yeast

Abstract: In humans, the frequency with which meiotic chromosome mis-segregation occurs increases with age. Whether age-dependent meiotic defects occur in other organisms is unknown. Here, we examine the effects of replicative aging on meiosis in budding yeast. We find that aged mother cells show a decreased ability to initiate the meiotic program and fail to express the meiotic inducer IME1. The few aged mother cells that do enter meiosis complete this developmental program but exhibit defects in meiotic chromosome segregation and spore formation. Furthermore, we find that mutations that extend replicative life span also extend the sexual reproductive life span. Our results indicate that in budding yeast, the ability to initiate and complete the meiotic program as well as the fidelity of meiotic chromosome segregation decrease with cellular age and are controlled by the same pathways that govern aging of asexually reproducing yeast cells.

Cell Polarity Determinants Establish Asymmetry in MEN Signaling

Abstract: Components of the mitotic exit network (MEN), a signaling pathway that triggers exit from mitosis, localize to the spindle pole body (SPB) that migrates into the daughter cell during anaphase but are largely absent from the SPB that remains in the mother cell. Through the analysis of one of the determinants of this asymmetry, Bfa1, we find that the machinery responsible for establishing cell polarity and cytoplasmic microtubules collaborate to establish MEN asymmetry. In cells defective in the Cdc42 signaling pathway or the formin Bni1, Bfa1 localizes to both SPBs. The quantitative analysis of Bfa1 localization further shows that Bfa1 can associate with both SPBs in a transient and highly dynamic fashion, but the protein is stabilized on the SPB that migrates into the daughter cell during anaphase through microtubule-bud cortex interactions. Our results indicate that mother-daughter cell asymmetry determinants establish MEN signaling asymmetry through microtubule-bud cortex interactions.

Decisions, decisions, decisions

Abstract: As I sit here in my soon-to-be-former home office, my mind is whirling with all the choices I have ahead of me. It's a bit overwhelming, if not outright intimidating. Still, decisions have to be made and not all of them will be easy. For the most part, our entire lives are actually based on decisions, be they good or bad. None of us has a crystal ball so sometimes it's impossible in the moment to tell how a decision is going to turn out. At the time, we may think it to be the smartest move that could be made. Other decisions and circumstances that occur in the days and years that follow that impact that earlier decision could cause us to question how smart it really was after all. Where is the Lord in the decision making process? James wrote, " If any of you lacks wisdom, let him ask of God, who gives to all liberally and without reproach, and it will be given to him. " (James 1:5). Does that mean that the Father is going to whisper the right decision in our ears? Does it mean that He is going to do something dramatic that makes the right decision so very clear that we'd have to be complete fools not to see it? Some believe this but this is not what James is saying. As much as we'd all like the Lord to make our decisions for us, the fact is that He has left our choices up to us. Again, where is the Lord in the decision making process? If He has promised to give us wisdom, how does He do it? Actually, He has already equipped each of us with the basics for making wise decisions in that He has given us brains that, along with the rest of our bodies, were " fearfully and wonderfully made. " (Psalm 139:14). Inside each of us is the basic processing unit necessary for determining right from wrong. We are not born with the capability of knowing the difference between the two, but instead grow into that capability Parents, teachers, friends, circumstances and other influences shape the principles that guide our decisions. For Christians, the Word of God acts as a governor on those worldly influences, causing us to stop and think about what God has said in the Bible before we act (James 3:17). Ideally, …