Joshua Heyza
Wayne State University, MI·Biochemistry·Early-career
DNA breaks that sever both strands of the double helix are among the most dangerous kinds of damage a cell can suffer: left unrepaired or repaired badly, they scramble chromosomes and destabilize the genome. Human cells handle these breaks with two main repair routes, homologous recombination, which copies the missing information from an intact sister chromosome and is accurate, and non-homologous end joining, which simply rejoins the broken ends and is faster but error-prone.
- Fields
Biochemistry
Genetics
Biology
- Topics
DNA double-strand break repair
homologous recombination
non-homologous end joining
- Grants
- 1 known grant, through Feb 2028
What they work on
- 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.
- Test whether MDC1 and its PST domain function specifically in transcription-coupled homologous recombination, mapping where MDC1 sits across the genome with chromatin immunoprecipitation sequencing.
- Generate MDC1 mutants that separate its roles, retaining non-homologous end joining while losing homologous recombination or the reverse, to isolate each repair pathway genetically.
- Define the genetic makeup of the MDC1-dependent homologous recombination pathway by combining these pathway-specific MDC1 alleles with genome-wide CRISPR screens.
More about the research
How a cell chooses between them, and how repair is coordinated with other things happening on the chromosome, is still incompletely understood. This project asks how one protein steers that choice.
Why it matters
Faithful repair of double-strand breaks is what keeps chromosomes intact, and failures of this system underlie genome instability. Working out how MDC1 directs breaks toward accurate homologous recombination, especially breaks that arise where genes are being transcribed, would supply a new model for how repair pathway choice is controlled in human cells and identify the genes that act with MDC1 in that route.
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.
Francesca Storici
Georgia Institute of Technology, GA·Genetics
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.
Zhiyuan Shen
Rutgers University-New Brunswick, NJ·Biochemistry
Reveal how chromatin context, shaped by methylation, sumoylation and ubiquitination tags, controls the recruitment and function of the BRCA1-PALB2-BRCA2 repair complex and regulators such as 53BP1, RNF4 and BARD1.
The school
Wayne State University: 21 labs on PI Pages, $292M a year on research, 194 research doctorates a year.
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