Robert J Duronio
University of North Carolina at Chapel Hill, NC·Genetics
Every time a cell divides, it must copy its entire genome accurately and then repackage that new DNA. Mistakes in this process contribute to many diseases, especially cancer.
- Fields
Genetics
Biology
Biochemistry
- Topics
DNA replication
chromatin
histone genes
- Grants
- 1 known grant, through Jul 2027
What they work on
- Determine what is required for the coordinated production of replication-dependent histone mRNAs, using biochemical and genetic approaches in Drosophila to test the role of the Histone Locus Body, the nuclear structure that assembles at clustered histone genes.
- Define how the Histone Locus Body contributes separately to transcription of histone genes and to processing of their unusual stem-loop-ended pre-mRNAs, which lack the poly-A tail of other eukaryotic messages.
- Use engineered Drosophila carrying mutations in histone N-terminal tails to block specific chemical modifications such as methylation, acetylation and phosphorylation, and test how each alters chromatin organization in the animal.
- Map how chromatin organization modulates DNA replication genome-wide, combining histone-tail mutant flies with cell biological imaging and next-generation DNA sequencing to locate changes in replication initiation and progression.
More about the research
Copying a genome as large as a human's means starting DNA synthesis at thousands of separate sites on each chromosome, and it also means making enormous amounts of histone proteins, the spools that DNA wraps around. This project asks how the packaging of DNA into chromatin (DNA plus its histone spools) shapes where and how well the genome gets replicated during animal development, using the fruit fly Drosophila melanogaster as a model.
Why it matters
Faithful DNA replication is what keeps genetic information intact as cells divide, and its breakdown underlies cancer and other proliferative disease. By pinpointing how histone supply and specific chemical marks on histone tails control where replication starts and how accurately it proceeds, this work could identify conserved control points relevant to human cells, since the proteins involved are nearly the same in flies and people.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Craig L Peterson
University of Massachusetts Chan Medical School, MA·Biochemistry
Define the step-by-step mechanism by which the SWR1C remodeler places the histone variant H2A.Z into nucleosomes, using ensemble and single-molecule fluorescence assays.
Kristen Johansen
Iowa State University, IA·Genetics
Test whether the histone marks H3K9me2, H3S10ph and H4K16ac jointly fine-tune gene expression by setting how permissive chromatin is for transcription, using non-dividing salivary gland cells from third-instar Drosophila larvae.
Stanislava Chtarbanova
University of Alabama, AL·Microbiology & Immunology
Determine whether older fruit flies survive Flock House Virus infection through infection tolerance, by changing their metabolism to limit damage, using genetic, molecular and metabolic methods.
The school
University of North Carolina at Chapel Hill: 72 labs on PI Pages, $1.6B a year on research, 523 research doctorates a year.
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