Human artificial chromosomes, or HACs, have been limited by their key component for years. Artificial centromeres should behave like their natural counterpart in replication processes. Centromeres are thought to be established at specific marks along human DNA; these epigenetic marks consist of proteins or chemical tags that are made of CENP proteins. This is where HACs fall short, the CENP-B proteins along with repetitive sequences prevent a reliable inheritance of HACs artificial centromeres. This is where Ben Black’s team of researchers at University of Pennsylvania have targeted their work.
Ben’s team has created two types of new HACs. Both do not have the CENP-B protein, and one even lacks the repetitive sequences. The first improvement noted was that by removing CENP-B protein, HACs could more reliably pass on genetic information. The replication process was still possible since Black’s team inserted epigenetic markers in the HACs manually. This new found reliability allowed for more opportunity to study genomic approaches.
Epigenetic markers are essential for natural chromosomes and HACs. CENP-B, however, is not required for HACs. This conclusion was derived by Black’s team guiding CENP-A, which is essential in both HACs and naturally occurring centromeres, to assemble on incoming HAC DNA.
The most remarkable success of this experiment is that there is no long repeating sequence in the functional chromosomes. This could open the door for a more reliable method to study longer sequences, and then fitting them into viruses; a popular approach to delivering synthetic genetics.