11.4 Replication of Eukaryotic Chromosomes

Question 1

What is the rate of DNA synthesis in human cells?

Answer 1

~50nt/sec

Question 2

Replicon?

Answer 2

DNA being replicated in both directions from one origin

Question 3

When are nucleosomes disassembled and reformed?

Answer 3

during DNA replication

Question 4

Explain how nucleosomes are disassembled and reformed during DNA replication.

Answer 4

DNA is packaged in nucleosomes within minutes of synthesis. A tetramer of H3 and H4 is associated with DNA, followed by two dimers of H2A and H2B. New nucleosomes are composed of recycled and new histones. Chromatin is open to histone modification just after replication.

Question 5

Briefly explain the process of replication

Answer 5

Each origin of replication binds proteins that unwind the two strands of the double-helix, forming a replication fork
As replication opens up a chromosome’s DNA, a replication bubble become visible
The DNA running both ways from one origin of replication to the endpoints, where is merges with DNA from adjoining replication forks = replication unit or replicon
This complex process also includes the synthesis and incorporation of histone and nonhistone proteins to regenerate nucleosomes and chromatin structure

Question 6

What are telomers?

Answer 6

they are “caps” that protect the ends of eukaryotic chromosomes. They consist of specific repetitive species-specific sequences (200-1500 repeats with variable numbers between different cell types) and don’t contain genes. (eg; TTAGGG in humans). They prevent chromosome fusions and maintain integrity of chromosomal ends.

Question 7

Replication at the ends of chromosomes

Answer 7

RNA primers used during DNA replication are removed, leaving unreplicated DNA at the 5’ ends. Without a special mechanism, DNA would be lost from every new DNA strand at each cell cycle.

Question 8

What is telomerase?

Answer 8

It is a ribonucleoprotein that extends telomeres.
Telomerase RNA is complementary to telomere repeat sequences. It serves as a template for the addition of new DNA repeat sequences to telomere. Additional rounds of telomere elongation occur after telomeres translocate to newly-synthesized end.

Question 9

Telomerase activity and cell proliferation:

Answer 9

In humans, the levels of telomerase and cellular life-span varies between different types of cells
Most somatic cells have low expression of telomerase
Telomeres shorten slightly at each cell division
Senescence after < 50 generations in culture
Germ cells, stem cells, and tumor cells have high expression of telomerase
At each generation, telomere length is maintained