Francesca Storici
Georgia Institute of Technology, GA·Genetics
A break that severs both strands of the DNA double helix is among the most dangerous things that can happen to a cell. Repaired badly, it leaves mutations, fuses the wrong chromosomes together, and can start a cell down the path to cancer.
- Fields
Genetics
Biochemistry
Biology
- Topics
DNA double-strand breaks
DSB repair
non-homologous end joining
- Grants
- 1 known grant, through Apr 2030
What they work on
- Build matched human kidney (HEK293T) and diploid retinal pigment epithelial (RPE-1) cell lines expressing spliced or non-spliced RNA from the same AAVS1 safe-harbor insertion site, and measure how each transcript changes end-joining repair of CRISPR/Cas9 breaks using deep sequencing.
- Identify the proteins driving RNA-mediated end joining by blocking core non-homologous end joining and microhomology-mediated end joining factors with chemical inhibitors and siRNAs, and define their effects on repair efficiency, fidelity, and pathway choice.
- Use CRISPR interference to selectively lower nascent spliced and non-spliced transcripts and test whether reducing the RNA itself reduces end-joining repair at the matching DNA break.
- Test whether transcript RNA affects repair differently in exons versus introns of endogenous human genes, comparing breaks induced by CRISPR/Cas9 with those caused by mutagens in both cell lines.
More about the research
Cells have several repair systems for these breaks, and decades of work have described the proteins involved. Far less is known about whether RNA takes part. Because RNA copies of genes carry sequences that match the DNA they came from, an RNA molecule sitting near a break could in principle line up with both broken ends and hold them together. This project asks whether that happens in human cells, and how.
Why it matters
If RNA transcripts routinely help repair broken chromosomes, they become a new class of target for controlling genome stability, relevant to cancers and degenerative diseases that arise from faulty repair. More immediately, the findings could improve genome editing, where the outcome at a cut site determines whether an edit is precise, and could inform strategies to limit mutation from DNA-damaging exposures.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Joseph J. Loparo
Harvard University, MA·Biochemistry
Determine how core and accessory non-homologous end joining factors cooperate to tether broken DNA ends, using single-molecule imaging of the synaptic complex in a physiological cell-free system.
Joshua Heyza
Wayne State University, MI·Biochemistry·Early-career
Determine what the intrinsically disordered PST repeat domain of MDC1 binds on chromatin and how phosphorylation regulates that tether, using molecular, biochemical and biophysical approaches together with live-cell single-molecule imaging.
Dale A Ramsden
University of North Carolina at Chapel Hill, NC·Biochemistry
Determine how Pol θ's interactions with the DNA-copying machinery, including the polymerase Pol δ and the DNA clamp PCNA, affect cells' need for Pol θ-mediated end joining.
The school
Georgia Institute of Technology: 50 labs on PI Pages, $1.5B a year on research, 572 research doctorates a year.
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