This week we profile a recent publication in Nature Communications from the laboratory of
Dr. Peter Lansdorp at the University of British Columbia.
Can you provide a brief overview of your lab’s current research focus?
My lab is exploring various applications of our single cell DNA template strand sequencing technique (Strand-seq). In our most recent Nature Communications paper we describe one of these applications: the mapping of sister chromatid exchange events. Previously, these events could only be studied using microscopy; with Strand-seq we can study these DNA repair reactions at a resolution that is orders of magnitude higher. We also had a paper in eLife late last year describing application of Strand-seq in yeast.
What is the significance of the findings in this publication?
This is the first study that reports on the location of sister chromatid exchange events (SCEs). In cells from patients with the cancer prone Bloom syndrome, where SCEs are roughly 10-fold more frequent than in normal cells, we found that SCEs map to active genes that have guanine-rich sequence motifs predicted to be capable of folding into stable guanine quadruplex (G4) structures.
What are the next steps for this research?
We would like to better understand the biological function of G4 structures and study the molecules and pathways that are involved in resolving G4 structures. We also want to map SCEs in cells with defects in other RecQ genes and study SCEs in cells following treatment with drugs that pose problems for DNA replication such as PARP inhibitors. I am looking for talented students and postdocs that are interested in these questions and can see the power of Strand-seq to address these questions.
This research was funded by:
This work was done by a talented graduate student, Niek van Wietmarschen, while I was in the Netherlands. The work was funded by an Advanced Grant from the European Research Council.
