Back to chapter

5.4:

Chromosome Structure

JoVE Core
Molecular Biology
A subscription to JoVE is required to view this content.  Sign in or start your free trial.
JoVE Core Molecular Biology
Chromosome Structure

Languages

Share

The DNA-histone complex contained in the nucleus is called chromatin and condenses to form chromosomes that consist of a single chromatid or sister chromatids – depending upon the cell cycle stage. A functional eukaryotic chromosome must have a centromere, a DNA sequence that links sister chromatids. The centromere is also where the kinetochores are constructed after the chromosome has replicated. These protein complexes allow the spindle microtubules to move the chromosomes around during cell division. Depending upon the location of the centromere, chromosomes can exist in four major configurations. In the metacentric configuration, the centromere is centered, resulting in arms of similar lengths. Whereas, in the submetacentric configuration, the centromere is off-center, resulting in arms of different lengths. In the telocentric configuration, the centromere is at the very end of the chromosome, resulting in long, single arms.  In acrocentric chromosomes, the centromere is located near the end, giving the appearance of a ‘stalk’ and ‘bulb’. These various configurations occur naturally, making them useful in identifying specific chromosomes. For example, the human Y chromosome is acrocentric.      Each chromatid must also have telomeres, which consist of non-coding repetitive nucleotide sequences, at their tips.  The telomeres protect and stabilize the ends of chromosomes. If a chromosome breaks, it will begin to degrade at the newly created end, which lacks a telomere.  Finally, a chromosome must have multiple origins of replication, sequences of nucleotides that determine where DNA replication begins.  Human chromosomes contain approximately 30,000 origins of replication in order to expedite the replication process. If a human chromosome only contained one origin of replication, it would take over a month to replicate a single chromosome.  When each chromosome replicates, beginning at multiple origins of replication, the resulting sister chromatids are held together at the centromere with telomeres at their tips.  Right before cell division, chromosomes are in their most condensed state. This is why observations of chromosomes are often made at this point in the cell cycle.

5.4:

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.

The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.

Telomeres consist of non-coding repetitive nucleotide sequences, at their tips. These sequences are typically similar across species. They usually consist of repeated units of adenine or thymine followed by multiple guanine nucleotides. Telomeres protect and stabilize the ends of chromosomes. If a chromosome were to break, it would begin to degrade at the newly created end, which lacks a telomere.

Origins of Replication and ARSs

Eukaryotic chromosomes must also have numerous origins of replication, which are sequences of nucleotides that determine where DNA replication begins. While the precise number of origins of replication in the human genome has yet to be quantified, at least 30,000 would be required in order for replication to occur in a timely fashion. If human chromosomes contained only one such origin, for example, it would take more than a month to replicate a single chromosome.

While the importance of origins of replication is established, defining these sequences has proven difficult. However, some experiments with yeast have identified a few candidates. When certain chromosomal sequences are added to a yeast cell as an extracellular, circular DNA molecule, they replicate autonomously. This gives these sequences their name – autonomously replicating sequences (ARSs). Some ARSs likely correspond to origins of replication that function within the yeast genome. However, some of these are not located along a stretch of DNA that is strongly associated with initiation of replication.

In mammals, such as humans, and other more complex eukaryotes, the origin of replication sequences are poorly defined. This is because they are likely defined by a combination of nucleotide sequence, associated proteins, and chromatin structure.

Suggested Reading

  1. Leonard, Alan C, and Marcel Méchali. “DNA replication origins.” Cold Spring Harbor perspectives in biology vol. 5,10 a010116. 1 Oct. 2013, doi:10.1101/cshperspect.a010116
  2. Chan, Clarence S., and Bik-Kwoon Tye. "Autonomously replicating sequences in Saccharomyces cerevisiae." Proceedings of the National Academy of Sciences 77.11 (1980): 6329-6333.