CONTROL OF MEIOTIC CHROMOSOME FRAGMENTATION
Dr. Gerben Vader
Current Position: Junior Group Leader, Max Planck Institute of Molecular Physiology, Department of Mechanistic Cell Biology.
2008-2012: (Postdoc) Whitehead Institute for Biomedical Research (advisor Prof. Andreas Hochwagen).
2002-2007: (PhD) Netherlands Cancer Institute/Utrecht University (advisors Prof. Susanne Lens/Prof. René Medema).
A chief focus of our laboratory is on understanding meiosis, the specialized cell division that is required for sexual reproduction. For this purpose we use the unicellular eukaryote Saccharomyces cerevisiae (i.e. budding yeast) to study how the meiotic cell division program allows the faithful generation of haploid gametes from a diploid progenitor cell. We are particularly interested in understanding meiotic chromosome fragmentation and repair. These events are essential to allow faithful meiotic chromosome segregation and sexual reproduction. Nonetheless, the introduction of hundreds of DNA double strand breaks critically endangers genome stability, and cells therefore invest significant energy in control systems that safeguard the genome during DNA break formation and repair. We study the mechanisms that operate to minimize potentially deleterious meiotic DSB repair events within repetitive DNA elements and centromere-proximal regions. We use a combination of yeast genetics, molecular biology and biochemical methodology to elucidate the molecular mechanisms that specifically act at these chromosomal loci. A specific focus of the lab is on the activity and regulation of Pch2TRIP13, an AAA+ ATPase that is involved in protecting repetitive DNA elements from unwanted DNA break formation. Recently, we have also initiated projects to study the role of the human homologue of Pch2TRIP13 during mitosis, with a specific focus on its described role in mitotic checkpoint signaling. For these studies, we employ cell biology in human cell culture systems coupled with biochemical and biophysical approaches. In total, we aim to shine light on the systems that act to minimize the destabilization of the genome during cell division.
Yeast genetics, molecular biology, cell biology, human cell culture, biochemistry
Vincenten N, Kuhl LM, Lam I, Oke A, Kerr ARW, Hochwagen A, Fung J, Keeney S, Vader G* and Marston AL*. The kinetochore prevents centromere-proximal crossover recombination during meiosis. eLife 2015, Dec 14;4, *equal contribution, co-corresponding author.
Vader G (2015). Pch2TRIP13: controlling cell division through regulation of HORMA domains. Chromosoma 2015, 124(3):333-9.
Vader G*, Blitzblau HG*, Tame MA, Falk JE, Curtin L, Hochwagen A. Protection of repetitive DNA borders from self-induced meiotic instability. Nature 2011, 477(7362), 115-9, *equal contribution.
Chen SY, Tsubouchi T, Rockmill B, Sandler JS, Richards DR, Vader G, Hochwagen A, Roeder GS, Fung JC. Global analysis of the meiotic crossover landscape. Dev Cell 2008, 15(3): 401-415.