Class Notes (977,101)
US (384,071)
UMN (3,756)
BIOL (152)
BIOL 4004 (13)
Lecture 1

BIOL 4004 Lecture Notes - E2F, P53, Microtubule

10 Pages
125 Views
Fall 2015

Department
Biology
Course Code
BIOL 4004
Professor
Matthes David
Lecture
1

This preview shows pages 1-3. Sign up to view the full 10 pages of the document.
MBC5 Study Guide – Chapter 17 (The Cell Cycle)
In this chapter, we will consider the mechanics of cell division (Mitosis and Cytokinesis)
and then examine the regulation of the cell cycle. In your book, the chapter is organized a bit
differently, but it makes more sense to understand the mechanics of cell division first, then to
discuss how those mechanics are regulated.
MITOSIS (Starting on p1071)
Mitosis is the process of nuclear division in eukaryotic cells. The primary event is the
sorting of sister chromatids into two separate sets of chromosomes, one set going to each of
two nuclei. In this section, we will examine the steps of this process, and consider the roles of
various proteins that are needed to organize and sort the chromosomes. The stages of mitosis
are described in Panel 17-1. You should already be familiar with these stages from previous
courses in General Biology and Genetics. You should review this panel if you need to as you
are expected to know this basic information.
M-Cdk Drives Entry into Mitosis
A protein kinase called M-Cdk is responsible for initiating mitosis (i.e. the cell cycle
transition from G2-phase into the Prophase stage of mitosis).
Dephosphorylation activates M-Cdk at the onset of mitosis
We will discuss the regulation of this kinase in detail later.
Cohesins Help Hold Sister Chromatids Together
Note: This section is on p1070. After DNA replication, the two copies of a chromosome are
held together as sister chromatids. A protein complex called cohesin is partly responsible for
holding the sister chromatids together. Knots between the DNA molecules (called DNA
catenations) of the sister chromatids also contribute to hold the sister chromatids together. In
sum, cohesin and DNA catenations are said to provide sister chromatid cohesion.
Condensins Help Configure Replicated Chromosomes for Segregation
Condensin is responsible for causing the sister chromatids to become compact. This occurs
after they have been replicated during prophase of M phase. The mechanism whereby
condensin affects chromosome structure is not known. Note that the condensin and cohesin
protein complexes are related to each other, and probably act in a similar manner. Figures 17-
24 and 17-27 provide hypothetic models for how they might act.
The Mitotic Spindle is a Microtubule-Based Machine
The structure that performs the sorting process of chromosome to daughter cells is the
mitotic spindle. The mitotic spindle is a large assembly of cytoskeletal, motor, and accessory
proteins that organizes the sister chromatids and segregates the chromosomes after the sister
chromatids have separated. In this chapter, we will consider the details of this process. A
schematic drawing of a spindle is shown in Figure 17-28. Three types of microtubules are
found:
1 • Astral microtubules radiate outward and play a role in positioning the spindle in
the cell.
2 • Overlap microtubules interdigitate the region where the chromosomes are found.
These play a role in pushing the two poles apart, after the chromatids have separated.
3 • Kinetochore microtubules are attached to individual chromatids.
In addition to microtubules, kinesins and dyneins play key roles in the sorting process. In this
section, we will examine the steps in mitosis and the roles of the key proteins.
Microtubule-Dependent-Motor Proteins Govern Spindle Assembly and Function
A key event that occurs early in mitosis is the separation of the centrosomes. The minus
ends of the microtubules are anchored in the centrosome (Figure 17-29). As microtubules are
formed from each centrosome, occasionally two microtubules, each from a different
centrosome will overlap (see Figure 17-30, 17-31, 17-34). Motor proteins can bind to these
sites and crosslink the region. In addition, the hydrolysis of ATP by the motor protein exerts
a force that pushes the two centrosomes farther apart. Thus, overlapping microtubules are
useful both in spindle organization and centrosome separation.
Two Mechanisms Collaborate in the Assembly of a Bipolar Mitotic Spindle
These two mechanisms are (1) Centrosome-based and (2) Kinetochore-based. The first
mechanisms simply means that the pair of centrosomes nucleate microtubules to organize
asters of microtubules with the –ve ends at the centrosomes and the +ve ends away from the
centrosomes. In other words, cells begin mitosis already with a pair of pre-formed spindle
poles. The second mechanism is to do with the fact that microtubules can also nucleate from
chromosomes and Kinetochores can stabilize the +ve ends of microtubules.
Centrosome Duplication Occurs Early in the Cell Cycle
In animal cells, the duplication of centrosomes is a critical event. The centrosome is the
microtubule-organizing center of the cell. As we will learn, each centrosome forms a pole
that directs chromosome sorting. The centrosome contains the γ-tubulin ring that nucleates
the minus ends of microtubules.
M-Cdk Initiates Spindle Assembly in Prophase
The main message here is that M-Cdk phosphorylates motors that are needed for spindle
assembly, such as kinesin-5. M-Cdk also phosphorylates lamins which leads to nuclear
envelope breakdown, which is required for the interaction of microtubules with the
chromosomes, and thus assembly of the bipolar spindle.
The Completion of Spindle Assembly in Animal cells requires Nuclear Envelope
Breakdown
We covered this above.
Microtubule Instability Increases Greatly at M Phase
Compared to interphase, the assembly and disassembly of microtubules is much faster
during M phase. This is termed dynamic instability. Rather than a few long microtubules,
the cell contains many short microtubules emanating from the centrosomes. The
phosphorylation of motor proteins and MAPs is largely responsible for this change. In
addition, catastrophins remove microtubule caps, which permits disassembly of a
microtubule.
Mitotic Chromosomes Promote Bipolar Spindle Assembly
Kinetochores Attach Chromosomes to the Mitotic Spindle
Kinetochore microtubule attachment is a dynamic, random process. Due to dynamic
instability, many microtubules assemble and disassemble during prophase. If a microtubule
happens to collide with a kinetochore, the microtubule binds to the kinetochore. Such a
microtubule doesn’t totally retract back to the centrosome. Instead, it remains attached to the
kinetochore throughout mitosis, although its length can change. Initially, the capture is
usually a lateral interaction, but eventually the plus end of the microtubule becomes affixed
to the kinetochore (see Figures 17-36, 17-37, 17-38, 17-39).
As the capturing process is taking place, the kinetochore microtubules lengthen and shorten.
Microscopically, the sister chromatids are seen to be tugged back and forth between the
poles. Eventually, the tug of war ceases, and the sister chromatids form a straight line at the
metaphase plate (Figure 17-43).
Microtubules Are Highly Dynamic in the Metaphase Spindle
Experimentally, if a labeled tubulin protein is incorporated into a kinetochore or overlapping
microtubule, it will eventually be lost at the minus end (see the progression in Figure 17-41).
(Note: this is a special property of these microtubules and typically doesn’t happen during
interphase). The dynamic instability that these microtubules exhibit involves growth and
disassembly at the plus end, and primarily disassembly at the minus end.
Bi-Orientation is Achieved by Trial and error
Several factors promote biorientation: (1) proper cohesion between the sister chromatids is
essential for allowing biorientation to occur; (2) microtubules must be highly dynamic in
order to search for and capture a kinetochore; (3) kinetochores are positioned in a back-to-
back fashion, thus favoring interaction with microtubules from opposite spindle poles; (4)
kinetochores also stabilize the +end of microtubules, making them less dynamics once
attached to the kinetochores; (5) Lastly, there is a “Trial and Error” mechanism, sometimes
called “Error Correction”. All this means is that biorientated chromosomes are mechanically
stable because the pulling forces (or tension) on each one of the pair of kinetochores are in
balance. The cell can detect when a pair of kinetochores are not under balanced tension, for
example if microtubules from the same pole are attached to the same kinetochore. In this case

Loved by over 2.2 million students

Over 90% improved by at least one letter grade.

Leah — University of Toronto

OneClass has been such a huge help in my studies at UofT especially since I am a transfer student. OneClass is the study buddy I never had before and definitely gives me the extra push to get from a B to an A!

Leah — University of Toronto
Saarim — University of Michigan

Balancing social life With academics can be difficult, that is why I'm so glad that OneClass is out there where I can find the top notes for all of my classes. Now I can be the all-star student I want to be.

Saarim — University of Michigan
Jenna — University of Wisconsin

As a college student living on a college budget, I love how easy it is to earn gift cards just by submitting my notes.

Jenna — University of Wisconsin
Anne — University of California

OneClass has allowed me to catch up with my most difficult course! #lifesaver

Anne — University of California
Description
MBC5 Study Guide Chapter 17 (The Cell Cycle) In this chapter, we will consider the mechanics of cell division (Mitosis and Cytokinesis) and then examine the regulation of the cell cycle. In your book, the chapter is organized a bit differently, but it makes more sense to understand the mechanics of cell division first, then to discuss how those mechanics are regulated. MITOSIS (Starting on p1071) Mitosis is the process of nuclear division in eukaryotic cells. The primary event is the sorting of sister chromatids into two separate sets of chromosomes, one set going to each of two nuclei. In this section, we will examine the steps of this process, and consider the roles of various proteins that are needed to organize and sort the chromosomes. The stages of mitosis are described in Panel 171. You should already be familiar with these stages from previous courses in General Biology and Genetics. You should review this panel if you need to as you are expected to know this basic information. MCdk Drives Entry into Mitosis A protein kinase called MCdk is responsible for initiating mitosis (i.e. the cell cycle transition from G2phase into the Prophase stage of mitosis). Dephosphorylation activates MCdk at the onset of mitosis We will discuss the regulation of this kinase in detail later. Cohesins Help Hold Sister Chromatids Together Note: This section is on p1070. After DNA replication, the two copies of a chromosome are held together as sister chromatids. A protein complex called cohesin is partly responsible for holding the sister chromatids together. Knots between the DNA molecules (called DNA catenations) of the sister chromatids also contribute to hold the sister chromatids together. In sum, cohesin and DNA catenations are said to provide sister chromatid cohesion. Condensins Help Configure Replicated Chromosomes for Segregation Condensin is responsible for causing the sister chromatids to become compact. This occurs after they have been replicated during prophase of M phase. The mechanism whereby condensin affects chromosome structure is not known. Note that the condensin and cohesin protein complexes are related to each other, and probably act in a similar manner. Figures 17 24 and 1727 provide hypothetic models for how they might act. The Mitotic Spindle is a MicrotubuleBased Machine The structure that performs the sorting process of chromosome to daughter cells is the mitotic spindle. The mitotic spindle is a large assembly of cytoskeletal, motor, and accessory proteins that organizes the sister chromatids and segregates the chromosomes after the sister
More Less
Unlock Document
Start your 2 week free trial

Only pages 1-3 are available for preview. Some parts have been intentionally blurred.

Unlock Document
Start your 2 week free trial
You're Reading a Preview

Unlock to view full version

Unlock Document
Start your 2 week free trial

Share with your friends

Get 2 friends to sign-up for a free trial as well, and get an additional free week

Next

You've reached the limit of 4 previews this month

Create an account for unlimited previews.

Already have an account?

Log In


OR

Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit