It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
In the more than six decades since the discovery of the double helix, there has been tremendous progress in understanding the biochemical mechanisms responsible for the precise and accurate duplication of the genome. However, despite the remarkable conservation of proteins and protein functions required for DNA replication across both prokaryotic and eukaryotic systems, we know comparatively little about the functional elements that direct DNA replication in higher eukaryotes. My research program is focused on understanding how the start sites of DNA replication are selected and regulated in the context of the local chromatin environment to maintain genomic stability and to ensure the accurate inheritance of genetic and epigenetic information. Failure to accurately regulate DNA replication may result in under or over replication of the genome and lead to genomic instability -- a hallmark of tumorigenesis.
Identification of chromatin remodeling activities that modulate origin function.
Role of epigenetic writers and readers in maintaining the DNA replication program and genome stability.
Development of experimental and computational approaches to predict cell cycle gene expression changes from chromatin occupancy data.
Nucleotide resolution maps of chromatin structure following induction of site specific DNA breaks
Spatiotemporal re-assembly of chromatin behind the replication fork.
Developing chromatin occupancy based methods for mapping quantitative trait loci.
The MacAlpine laboratoy has diverse research interests from chromosome to computational biology. We have or have had graduate trainees from many of the graduate programs at Duke, including pharmacology, molecular cancer biology, cell and molecular bioliogy, genetics and genomics and computational biology.