Transition of DNA double-strand breaks to genetic crossovers

Since more than 10 000 years humans are growing crop plants, selecting for local adaption, high yields and further traits to deliver food security. These efforts are still ongoing, now framed by well controlled plant breeding programs. Though, it has long been recognized that not all beneficial traits of a certain crop species, present in various sub-species, can be combined in the same individual plant. Only recently, the molecular base for this impediment starts to emerge, relating to specific processes during meiosis. Meiosis is a specialised cell division that ensures the reduction of the genome prior to the formation of generative cells. During meiosis, novel combinations between parts of paternal and maternal chromosomes are generated through the process of homologous recombination (HR). A pre-requisite for HR are DNA double strand breaks (DSBs). Previously, a lot of effort has been dedicated towards understanding the determinants and the mechanisms of meiotic DSB formation and members of the given MEIOREC consortium contributed significantly. While meiotic DSBs are essential for subsequent exchange of parental genetic information, less than 10% of meiotic DSBs actually constitute such an exchange point. It is not understood, how the fate of a DSB at a certain genomic locus is determined and hence what limits the maturation of a meiotic DSB into a genetic exchange point, a cross-over (CO). The MEIOREC researchers have harnessed a research program to remedy this shortcoming of understanding and will experimentally address various aspect of the DSB-to-CO transition. In support of the overall aims, the group of Dr. Schlögelhofer, based at the Max F. Perutz Laboratories of the University of Vienna, provides a crucial molecular tool, already available prior to the project start. Using Arabidopsis thaliana as a model system, they have designed a fusion protein that allows the formation of artificial meiotic DSBs at desired genomic loci. These lead to significant increases in genetic exchange rates at these loci and now allows systematic and quantitative investigation of those factors and conditions that promote maturation of meiotic DSBs into COs. The group of Dr. Schlögelhofer will focus on the early events following meiotic DSB formation to understand how meiotic DNA is processed and how DNA repair proteins are loaded at the DNA DSB site. Ultimately the gained knowledge will allow to tap into the rich resources of nature to generate more variety of genetic combinations in crop plants for faster breeding progress.

Since more than 10 000 years humans are growing crop plants, selecting for local adaption, high yields and further traits to deliver food security. These efforts are still ongoing, now framed by well controlled plant breeding programs. Though, it has long been recognized that not all beneficial traits of a certain crop species, present in various sub-species, can be combined in the same individual plant. Only recently, the molecular base for this impediment starts to emerge, relating to specific processes during meiosis. Meiosis is a specialised cell division that ensures the reduction of the genome prior to the formation of generative cells. During meiosis, novel combinations between parts of paternal and maternal chromosomes are generated through the process of homologous recombination (HR). A pre-requisite for HR events are DNA double strand breaks (DSBs). Previously, a lot of effort has been dedicated towards understanding the determinants and the mechanisms of meiotic DSB formation and members of the given MEIOREC consortium contributed significantly. While meiotic DSBs are essential for subsequent exchange of parental genetic information, less than 10% of meiotic DSBs actually constitute such an exchange point. It is not understood, how the fate of a DSB at a certain genomic locus is determined and hence what limits the maturation of a meiotic DSB into a genetic exchange point, a cross-over (CO). The MEIOREC researchers have harnessed a research program to remedy this shortcoming of understanding and have experimentally addressed various aspect of the DSB-to-CO transition. In support of the overall aims, the group of Dr. Schlögelhofer, based at the Max Perutz Laboratories of the University of Vienna, generated a molecular tool to investigate meiotic DSB formation and CO transition in depth. Using Arabidopsis thaliana as a model system, they have designed a series of fusion protein that allow the formation of meiotic DSBs at targeted genomic loci. These lead to significant increases in genetic exchange rates at these loci and now allow systematic and quantitative investigation of those factors and conditions that promote maturation of meiotic DSBs into COs. The group of Dr. Schlögelhofer furthermore investigated the meiotic DSB machinery in plants and its specific characteristics. Finally, they investigated the fate of meiotic DNA repair in specific genomic regions that must not recombine to yield successful offspring. The genomic regions that encode components of an essential cellular machine (the rRNA of ribosomes) is encoded in multiple repeats which need to be maintained. The Schlögelhofer group established that a non-canonical DNA repair mode specifically protects these regions from the otherwise important meiotic recombination. Ultimately the gained knowledge will allow to tap into the rich resources of nature to generate more variety of genetic combinations in crop plants for faster breeding progress.