The Role of Centromere Function in Human Artificial Chromosome Formation

Loading...
Thumbnail Image
Degree type
Doctor of Philosophy (PhD)
Graduate group
Biochemistry and Molecular Biophysics
Discipline
Biology
Biology
Engineering
Subject
Artificial Chromsomes
Cell Division
Centromere
Cloning
Human Genome
Synthetic Biology
Funder
Grant number
License
Copyright date
2023
Distributor
Related resources
Author
Gambogi, Craig, W.
Contributor
Abstract

The ability to synthesize large DNA assemblies has led to milestone achievements in prokaryotic systems and budding yeast chromosome biology motivating efforts to develop synthetic chromosomes in mammalian systems. Chromosomes in mammals and many other eukaryotes control their inheritance through an epigenetic locus: the centromere. Harnessing centromere epigenetics permits human artificial chromosome (HAC) formation but is not sufficient to avoid rampant multimerization of the initial DNA molecule that is introduced. Here, we describe an overhauled approach that efficiently forms stable, single-copy HACs. Their single-copy nature is achieved by starting with a construct that is sufficiently large to house the distinct chromatin types present at the inner and outer centromere. These HACs harbor full centromere function without the need to initially multimerize, thus permitting faithful chromosome engineering in the context of metazoan cells.

Advisor
Black, Ben
Date of degree
2023
Date Range for Data Collection (Start Date)
Date Range for Data Collection (End Date)
Digital Object Identifier
Series name and number
Volume number
Issue number
Publisher
Publisher DOI
Journal Issue
Comments
Recommended citation