MCB Lecture 19 Cell Cycle, Centromeres, DNA Damage and repair Flashcards
Describe the overall chromosome structure throughout interphase and mitosis
During interphase, the chromosome is compacted to a much lesser extent
During mitosis it is very compacted
What are the phases of the cell cycle?
G1
S
G2
M
What are the structural requirements of a chromosome?
2 telomeres
1 centromere
Many origins of replication
What can abnormalities in centromere number lead to? Give two examples
Problems with chromosome segregation
No centromeres: the chromosomes will segregate randomly
Two centromeres: two spindles will attach from each pole
The chromosome will break because it is being pulled by two different spindles
What type of DNA are centromeres made up of?
The centric region has a H3 histone variant
The peri centric region is heterochromatin: ie very dense
How many repeats of satellite DNA are there in general in a centromere?
1500-3000
Compare human centromeres with those in other organisms
Those in humans are much longer regions of DNA and have many repeats
Simpler organisms have more unique sequences but they are shorter
Describe the chromatin in centromeres. How does it differ from normal chromatin?
The chromatin in centromeres has a H3 variant
CENP-A
As well as
H3K9me2 in the peri centric chromosome
Why does centromere chromatin differ? What is its function?
The CENP-A variant binds to the kinetochore protein that must associate with centromeres.
What is special about the peri centric chromatin in centromeres?
It is very dense; dimethylated
Conventional heterochromatin modifications: H3K9me3
What happens if a centromeres function is lost?
A neocentromere can form from a previously inactive centromere
What are the requirements for a centromere in terms of definition?
It must have mitotic spindle attachments
Alpha-satellites are not vital for the attachment of spindle, so it is thus not in the definition
- heterochromatin
- H3K4me2 (centric, non kinetochore binding)
- CENP-A
What is a robertsonian translocation?
What sort of chromosomes does this occur in?
This is when two different chromosomes break at the centromere and reattach to the wrong one
Acrocentric chromosomes
What can happen to the centromere in a robertsonian translocation? (3)
Fusion
One lost: only one chromosome
Inactivation of one of them
What is normally on the p arm of the chromosomes that undergo Robertsonian Translocation?
rRNA and tRNA information that is present elsewhere in the genome. Thus it is not so dire if this is lost
What disorders can arise from Robertsonian Translocations?
Describe how this may occur
Trisomy 21
One of the parents has a Robertsonian translocation between cr. 21 and another Afrocentric chromosome
When this individual produces gametes, there is the possibility of having two copies of the q arm of chromosome 21 because it is fused onto the q arm of the other chromosome
In fertilisation, the individual will now have three copies, because another is received from the other parent
What is a replication origin?
This is the region where DNA replication starts
How many replication origins does a eukaryotic cell have?
Many
Origins of replication are … rich
AT
Describe the process of initiation of replication
- ORC protein complex binds to the AT region
- Cdc6 and Cdt1 associate
- Mcm associates
We now have the prereplicative complex - Cdk phosphorylates cdc6, and it dissociates, also cdt1
- The helix unzips and is replicated
Describe the process of elongation of DNA Replication
Name all the enzymes
Helicase Primase DNApol III RNA pimer Topoisomerase ssBP Ligase connects Okazaki fragments DNA pol I
What is a telomere?
It is a repetitive region on the end of chromosomes
It prevents degradation of the chromosome during DNA replication
What is the structure of telomerase?
How does this relate to function?
RNA part and protein part -> ribonucleoprotein
The RNA section provides a template for telomere synthesis
The protein part reverse transcribes DNA from the RNA template in the telomerase
TERT
What is the repeating DNA sequence in telomeres?
TTAGGG
