Human artificial chromosomes (HACs) could be useful tools for both understanding how mammalian chromosomes function and creating synthetic biological systems, but for the last 20 years, they have been limited by an inefficient artificial centromere. In the, researchers announce that they have made progress on this key component.
The centromere used to be called the black box of the chromosome; In mammals, centromeres the central point of the X-shaped chromosome ensure that a chromosome is inherited when a cell divides, acting as an anchor for the spindle fibers that pull the duplicated chromosome in half. The genetic sequence of a natural human centromere is thousands of repetitions of a 171-base-pair sequence.
Mammalian chromosomes function
Centromeric DNA must also be modifying epigenetically in the cell to function properly. These epigenetic marks (protein and chemical tags along the DNA) are thinking to be establishing at centromeres by the human CENP proteins. First-generation HACs have relied on both the repetitive centromere sequence and CENP-B. But the repetitive sequence make centromeres tricky to clone for study in the lab.
Therefore, “all of the synthetic chromosomes; that have been recently reporting use approaching that intentionally remove repetitive elements making it so far impossible to transition the techniques that work in yeast artificial chromosomes to HACs. Black’s team has now created two new HACs; neither use CENP-B, and one is not repetitive.
Cell with epigenetic markers
We wanted to see if we can break the rules by bestowing the DNA; we put into the cell with epigenetic markers from the get go. Their improvements remove the requirement for CENP-B, make the HACs more reliably inheriting in cell culture; and providing the opportunity for the researchers to study them with genomic approaching; which had previously been impossible.
CENP-B, though not essential for natural chromosomes, has been assuming to be requiring for artificial centromere formation until now. A closely related protein, CENP-A, is actually the essential epigenetic marker for centromeres; and Black and his team have been able to direct the assembly of CENP-A onto the incoming HAC DNA. The next-generation HACs made by Black and his team; will allow for more thorough study of the essential components of functional chromosomes.