Genetics + Genomics

Leveraging a novel system designed to examine the double-strand DNA breaks that occur as a consequence of gene amplification during DNA replication, Whitehead Institute scientists are bringing new clarity to the causes of such genomic damage. Moreover, because errors arising during DNA replication and gene amplification result in chromosomal abnormalities often found in malignant cells, these new findings may bolster our understandings of certain drivers of cancer progression.

Scientists have applied a new method of analyzing cell states to identify a gene required for breast stem cells to differentiate. This gene, RUNX1, is deregulated or mutated in some leukemias and breast cancers. The novel approach, known as PEACS, could also be used to screen for drugs that activate or inhibit the expression regulators of stem cell differentiation.

Biologists at Whitehead Institute and MIT have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors.

Although the genome editing system known as CRISPR/Cas has revolutionized genetic research in cell lines, its overall efficiency has been relatively poor when used to generate genetically altered animals for disease modeling.  Now Whitehead Institute scientists have altered the approach in a manner that could accelerate the production of mice carrying precise mutations of multiple genes.

A team of Whitehead Institute scientists has discovered the surprising manner in which an enigmatic protein known as SUUR acts to control gene copy number during DNA replication. It’s a finding that could shed new light on the formation of fragile genomic regions associated with chromosomal abnormalities.  

Scientists have long theorized that the way in which the roughly three meters of DNA in a human cell is packaged to fit within a nuclear space just six microns wide, affects gene expression. Now, Whitehead Institute researchers present the first evidence that DNA structure does indeed have such effects—in this case finding a link between chromosome structure and the expression and repression of key genes.

Deploying sophisticated high-throughput sequencing technology, dubbed ψ-seq, a team of Whitehead Institute and Broad Institute researchers collaborated on a comprehensive, high-resolution mapping of ψ sites that confirms pseudouridylation, the most common post-transcriptional modification, does indeed occur naturally in mRNA.

The protein CENP-A, which is integrated into human DNA at the centromere on each chromosome, has a vital role in cell division. Work from Whitehead Institute Member Iain Cheeseman’s lab describes how the vital and tightly controlled replenishment of CENP-A progresses.