Chromatin

How cells faithfully propagate chromosomal states epigenetically remains a major mystery. DNA methylation in Cryptococcus neoformans is propagated epigenetically, due to the ancestral loss of a de novo methylase (>50 Mya ago — wow!). We identified the first maintenance DNA methylase in the fungal/protist kingdoms, a remarkable ATP-dependent CpG methylase called Dnmt5. With collaborators we have characterized this methylase using a combination of genetics, biochemistry and high-resolution cryoEM structures. We seek to understand how it cooperates with the inheritance of H3K9me-modified histones to propagate epigenetic memory. We are focusing on events that occur at the replication fork.