Chromosomes lecture (LEARN)

Question 1

objectives

Answer 1

To provide an overview of the main structural features of chromosomes and to consider how the genome is packaged into chromatin.
Learning Objectives
* Understand how DNA is packaged into chromatin and describe the structure and function of histones.
* Understand that chromosome structure changes at different phases of the cell cycle.
* Understand the structure-function relationships of telomeres, centromeres, replication origins and kinetochores.
* Understand that non-protein-coding DNA exists in the genome and be able to describe characteristics of repeated DNA elements.
Describe the different types of eukaryotic transposable elements and their replication and transposition mechanisms.

Question 2

How is DNA packaged into chromatin?

Answer 2

Here are the key steps in the packaging of DNA into chromatin:

1 -Chromatin contains units called nucleosomes, which consist of DNA wrapped around histone proteins. Histones are small, positively charged proteins that form an octamer (a complex of eight proteins), around which DNA is wound.

2- Nucleosome Formation:
DNA wraps around the histone octamer in a left-handed helical turn, forming the nucleosome.

3- Linker DNA:

Linker DNA between nucleosomes connects one nucleosome to the next. This linker DNA plays a role in chromatin structure.

4 - 30-nm Fiber Formation:
Nucleosomes are further compacted into a structure known as the 30-nm chromatin fiber. The process involves additional coiling and folding of the nucleosomal array.

5 - Loop Domains:
The 30-nm fiber is organized into loop domains, forming loops anchored to the nuclear scaffold/matrix. This organization helps to organize and segregate different regions of the genome.

6 - Chromatin Compaction:
As cells progress through the cell cycle, chromatin undergoes dynamic changes in compaction. During cell division, chromatin condenses even further to form visible chromosomes.

Question 3

Describe the structure of histones

Answer 3

-Histones are small, positively charged proteins with a globular domain and an unstructured, flexible N-terminal tail

• There are five main classes of histones known as core histones, and they form the nucleosome structure. Each nucleosome consists of an octamer of core histones around which DNA is wrapped. The H1 histone is involved in linking adjacent nucleosomes.

-Core histones have a common structural motif known as histone fold, which consists of three alpha helices connected by two loops.

• The N-terminal tails of histones extend outward from the nucleosome and are subject to various post-translational modifications, such as phosphorylation.
  These modifications play a role in regulating chromatin structure and gene expression.

Question 4

Understand that chromosome structure changes at different phases of the cell cycle.

Answer 4

G1 Phase:

Chromosome Structure:
* During the G1 phase, chromosomes exist in a less condensed state known as chromatin.
* Chromatin is a complex of DNA, histones, and other proteins.

Activity: The cell is preparing for DNA replication, and gene expression is active. The chromatin is relatively open, allowing for transcription and other cellular processes.

2. S Phase (Synthesis):

Chromosome Structure:
*DNA replication occurs during the S phase. Each chromosome replicates to form two sister chromatids connected by a centromere.
*The chromatin becomes more condensed as the amount of DNA doubles.

Activity: The cell is actively synthesizing DNA, resulting in the formation of identical sister chromatids. The centrosomes also replicate.

3. G2 Phase:

Chromosome Structure:
*Chromosomes are composed of two sister chromatids, and the chromatin becomes more compact. *The nuclear envelope is intact.

Activity: The cell checks for DNA damage and completes preparations for mitosis.
*Cellular organelles and structures continue to duplicate.

4. Mitosis (M Phase):

Prophase:

Chromosome Structure:
* Chromosomes further condense, becoming visible under a microscope.
* Each chromosome consists of two sister chromatids.
* The nuclear envelope breaks down, and mitotic spindles form.

Activity:
* The mitotic spindle apparatus begins to organize, and microtubules attach to the centromeres of sister chromatids.

Metaphase:
Chromosome Structure:
* Chromosomes align at the metaphase plate, a central plane within the cell.
*The spindle fibers attach to the centromeres of each chromatid.

Activity: The cell ensures proper alignment of chromosomes before proceeding to the next phase.

Anaphase:
Chromosome Structure:
* Sister chromatids are separated and pulled toward opposite poles of the cell.
* Each chromatid is now considered an individual chromosome.

Activity: The mitotic spindle fibers contract, separating chromatids and ensuring equal distribution of genetic material.

Telophase:
Chromosome Structure:
* Chromatids reach opposite poles, and new nuclear envelopes form around each set of chromosomes.
* Chromosomes begin to decondense back into chromatin.

Activity: The cell prepares for cytokinesis, the division of the cytoplasm.

5. Cytokinesis:
   Chromosome Structure:
   * The cell divides into two daughter cells, each with its set of chromosomes.
   * The chromosome structure is in the form of decondensed chromatin

Activity: The cell cycle is complete, and each daughter cell enters the next G1 phase.

Question 5

Explain the structure-function relationships of telomeres, centromeres, replication origins and kinetochores

Answer 5

Telomeres
Structure:
* Telomeres are specialized structures at the ends of linear chromosomes.
* Telomeres consist of repetitive DNA sequences
* Telomeric DNA forms a loop structure called a t-loop, which helps protect the end of the chromosome.
Function:
* Telomeres protect the ends of chromosomes from degradation and fusion.
* Telomeres play a role in maintaining chromosome stability and preventing loss of genetic information during DNA replication.

Centromeres
Structure:
* Centromeres are specific DNA regions on chromosomes where kinetochores assemble.
* Centromeres contain repetitive DNA sequences, including the highly conserved centromere protein-binding region.
Function:
* Centromeres are essential for proper chromosome segregation during cell division.
* Centromeres provide a site for the assembly of kinetochore, a protein complex that attaches to spindle fibers during mitosis and meiosis.
* Centromeres ensure accurate distribution of genetic material to daughter cells.

Replication Origins
Structure:
* Replication origins are specific DNA sequences where DNA replication begins.
* Replication origins typically contain DNA elements recognized by initiator proteins and other replication initiation factors.
Function:
* Replication origins initiate the process of DNA replication.
* DNA replication begins bidirectionally from replication origins, forming two replication forks.
* Multiple replication origins exist on eukaryotic chromosomes to ensure efficient and timely replication.

Kinetochores
Structure:
* Kinetochores are protein structures located at the centromere of chromosomes.
* Kinetochores consist of multiple protein subunits, including those that bind to centromeric DNA.
Function:
* Kinetochores play a crucial role in attaching chromosomes to spindle fibers during mitosis and meiosis.
* Kinetochores mediate the interaction between chromosomes and microtubules of the mitotic spindle.
* Kinetochores ensure accurate segregation of chromosomes to daughter cells during cell division.

Question 6

Summary

Answer 6

Nucleosomes are the building blocks of chromatin. Nucleosomes permit reversible unfolding and compaction of chromatin. The is needed to:
1 - allow gene transcription and DNA replication
2 - Package DNA into the nucleus and allow faithful segregation of the genome into daughters of dividing cells

Each linear chromosome has 2 telomeres, a centromere and origins of replication.
Telomeres prevent loss of DNA sequences from chromosomal ends
Centromeres mediate chromosome attachment to the mitotic spindle via the kinetochore

Genomes of more complex organisms have huge numbers of repeated DNA sequence elements - transposable elements

DNA transposons, retroviral retrotransposons and polyA transposons are mobile genetic transposable elements, defective versions of which make up almost half of the human genome

Question 7

understand that non-protein-coding DNA exists in the genome

Answer 7

In the genome, non-protein-coding DNA refers to segments of DNA that do not directly code for proteins e.g. DNA elements

Question 8

describe characteristics of repeated DNA elements.
List and describe the 3 types

Answer 8

• Almost half of human genome is made up of repeated DNA elements
• Transposons are types of repeated DNA elements and there are 3 types:
  
  • 1 - DNA Transposons; Encode transposase enzyme which allows them to move around the genome in a cut and paste mechanism
  • 2 - retroviral retrotransposons; Replicate via RNA intermediates, producing new DNA copies that integrate at new genomic locations using reverse transcriptase
  • 3 - non retroviral polyA retrotransposons; replicate via RNA intermediates using reverse transcriptase
  Transposons can jump around the genome hence the name mobile genetic elements

Question 9

Describe the characteristics of DNA Transposons

Answer 9

Encode transposase enzyme which allows them to move around the genome in a cut and paste mechanism