ARS Elements, Centromeres, and Telomeres

ARS Elements, Centromeres, and Telomeres

Survival of a chromosome requires three basic properties–replication, proper segregation upon DNA replication and cell division, and replication and protection of the ends of the chromosome. Multiple origins of replication exist in the chromosomes of cells. These origins are called autonomously replicating sequences, ARS, because they can be cloned into DNA that will replicate on its own in other cells. Such DNA, however, does not properly partition itself into daughter cells because it lacks the necessary signals for segregation. Frequently the daughters fail to receive a copy of the DNA replicating under ARS control.

Classical cell biology has identified the portion of the chromosome that is responsible for segregation of the chromosomes into daughter cells. This is the centromere. As cells divide, the centromeres are pulled into the two daughter cells by microtubules. It has been possible to identify a centromere by seeking a DNA segment from a chromosome that confers the property of more correct segregation on a DNA element containing an ARS element.

A third necessary part to a normal chromosome is the telomere. Telomeres also have been identified by classical biology as being special. First, most chromosomes of eukaryotic cells are linear. This poses a problem in DNA replication as the normal DNA polymerase cannot elongate to the ends of both strands because it replicates only in a 5’ to 3’ direction. The end of one strand can’t be reached. Something else must extend the portion of the strand that cannot be completely repli - cated. Secondly, since chromosome breakage occasionally occurs, and has dire consequences to cells, they have evolved a way to try to rescue broken chromosomes by fancy recombination processes. The normal ends of chromosomes are inert in these rescue processes by virtue of special markers called telomeres. These telomeres have been identified by their properties of permitting the existence of linear artificial chro-mosomes that contain ARS elements and centromeres. Interestingly, telomeres are repeated sequences of five to ten bases, largely of C’s and G’s. A special enzyme adds these sequences onto single-stranded DNA possessing the same telomeric sequence. These unusual enzymes must first recognize the sequence to which they will make additions, and then they add nucleotides, one at a time, to generate the correct telomeric structure. They do this making use of an internal RNA molecule that provides the sequence information needed for the additions.