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‘A trip to the evolutionary repair shop: how cells adapt to the loss of important proteins’
September 13, 2019 @ 11:00 am - 12:00 pm
Professor Andrew Murray
Harvard University
‘A trip to the evolutionary repair shop: how cells adapt to the loss of important proteins’
Abstract:
We are intrigued by the idea that loss of function mutations are an important generator of evolutionary diversity. If this fantasy were true, such mutations would be likely to produce both benefits (e.g. access to novel niches) and costs (reduced proliferation or survival). If the costs can be rapidly diminished, by accumulating suppressor mutations, such hopeful monsters might be an important source of evolutionary novelty and account for the loss of “universal functions” in certain branches of the tree of life (e.g. the absence of the anaphase promoting complex in Giardia). I will discuss two projects that ask how cells to evolve to deal with the loss of important components. In the first, we removed Ctf4 a subunit of the replisome, the complex that holds various components of the replication fork together. Over 1000 generations, cells recover to almost wild type growth rates and do so by accumulating mutations in three pathways: they inactivate the DNA damage checkpoint, they slow down replication forks, and they increase the loading of cohesin, the protein complex that holds sister chromosomes together until the end of mitosis. In the second, we focus on kleisin, part of the cohesin complex, and the subunit that is cleaved to allow sister chromatid separation at anaphase. Expressing the meiotic cohesin in the mitotic cell cycle leads to defects in sister chromatid cohesion and evolving cells to grow better requires three types of mutations: inactivating the transcriptional mediator complex, making mutations in other components of cohesin and the protein that cleaves it, and slowing progress through G1. We will, as usual, speculate extensively on the basis of limited experimental data!
Friday, Sept 13th, 2019
11:00 a.m
Ramsay Wright, 432
Host: John Calarco: john.calarco@utoronto.ca