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Lecture 12

Lecture 12: "Actin Filaments - Microfilaments"

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Western University
Biology 2382B
Robert Cumming

Cell Biology Lecture No. 12: Actin Filaments – Microfilaments th Monday February 25 , 2013 LECTURE 11 CONT’D The Centromere & Spindle Formation: The centromere is the constricted DNA sequence required for proper segregation of chromosomes during mitosis and meiosis and is the region of mitotic chromosomes where the kinetochore forms. It is the outer kinetochore and inner kinetochore proteins that constitute the kinetochore and mediate the attachment of chromosomes to microtubules. Microtubules are captured away from the outer kinetochore. This is so the microtubule plus-end can be assembled and disassembled easily. The correct capture and congression of chromosomes involves all chromosomes being captured by microtubules and all chromosomes aligning during metaphase (checkpoints of mitosis involving microtubules). As a microtubule captures the outer kinetochore of a chromosome, there is a stabilization of plus-end growth, which achieves greatest stability when the chromosome is captured by microtubules from both sides. -During alignment or congression, the now bi-oriented chromosomes then move to a central point between the spindle poles. Note that during these steps chromosome arms point away from the closest spindle pole: this is due to kinesin-4 motors on the chromosome arms moving toward the plus-ends of the microtubules. Congression also involves bidirectional oscillations of chromosomes, with one set of kinetochore microtubules shortening on one side of the chromosomes and the other set lengthening on the other. On the shortening side, a kinesin-13 protein stimulates microtubule disassembly and a dynein-dynactin complex moves the chromosome toward the pole. On the side with lengthening microtubules, kinesin-7 protein holds on to the growing microtubule. Tension & Ndc80 Proteins: -Tension assures bi-orientation (that the chromosome is attached to both spindle poles), which is important in providing fully-stable microtubule plus-ends. Ndc80 is a kinetochore protein that when phosphorylated leads to microtubule instability. Under no tension, the phosphorylation of Ndc80 proteins at the kinetochore results in weak microtubule interactions with the kinetochore. Chromosomal Movements In Anaphase (A & B): -Both anaphase A and B (with respect to microtubules) occur simultaneously: Anaphase A requires microtubule shortening (d
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