Convergent genes shape budding yeast pericentromeres

Marston lab paper featured in Nature.

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Image from Marston lab Nature paper 2020
The three-dimensional structure of pericentromeres in budding yeast is defined by convergent genes which mark pericentromere borders and trap cohesin complexes loaded at centromeres, generating an architecture that allows correct chromosome segregation.

Authors

Paldi, F., Alver, B., Robertson, D., Schalbetter, S.A., Kerr, A., Kelly, D.A., Baxter, J., Neale, M.J., and Marston, A.L.

Summary of Paper by Lori Koch

Every living organism is composed of cells, each which contain strands of DNA that have all of the information to build and maintain the cell. The DNA strands are packaged into more compact structures called chromosomes. When a new cell is made in the process of cell division, the chromosomes are replicated and the copies shuttled into a new cell. To be inherited properly, each chromosome must attach to dynamic protein fibres called microtubules that pull the chromosomes into the new cell. The microtubules attach to the DNA in chromosomes through proteins that bind to a special place on each chromosome called the centromere. In their recent study, PhD student Flora Paldi in Adele Marston's lab in the Wellcome Centre for Cell Biology and their colleagues found that the 3D structure of the pericentromere, the region immediately surrounding the centromere itself, is important for proper chromosome segregation during cell division. Specifically, through a cutting-edge structure-reconstruction method called Hi-C (a variant of the 3C "chromosome conformation capture" technique), the authors found that chromosomes have a loop on either side of the centromere during the early stages of cell division. These loops then disappear as the chromosomes come under tension in the process of microtubule attachment just before chromosome segregation. Next, they discovered that the order of genes on the chromosome determined the size of these loops. Making the loops larger through genetic manipulation prevented chromosomes from being segregated properly. They measured this by tracking whole-chromosome inheritance with fluorescence imaging. Overall, the study demonstrates that the 3D structure of chromosomes, established by both DNA and proteins, is very important for chromosome inheritance.

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Image model from Marston lab Nature paper 2020
Model from paper

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