Seminars

Ronald T. Hay - Centre for Gene Regulation and Expression, University of Dundee

WT PhD programme seminar - Decoding the SUMO Signal

Small Ubiquitin-like Modifier (SUMO) emerged from the shadow of the well-established ubiquitin some 15 years ago when it was shown that a distinct conjugation pathway was responsible for SUMO modification. Since then it has been established that SUMO modifies over a thousand substrates and plays diverse roles in many important biological processes. Recognition of SUMO is mediated by short peptide sequences known as SUMO Interaction Motifs (SIMs) that allow effector proteins to engage SUMO modified substrates. Like ubiquitin, SUMO can form polymeric chains and these chains can be recognized by proteins containing multiple SIMs. One protein that contains such a sequence of SIMs also contains a RING domain that is the hallmark of a ubiquitin E3 ligase. This ubiquitin ligase known as RNF4 has the unique property that it can recognize SUMO modified proteins and target them for ubiquitin mediated proteolysis. Structural and biochemical analyses of RNF4 has shed light on the long sought after mechanism of ubiquitin transfer and illustrates how its RING domain primes the ubiquitin loaded E2 for catalysis.

Plechanovová A, Jaffray EG, Tatham MH, Naismith JH, Hay RT. (2012)  Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis.  Nature 489, 115-120

Plechanovová A, Jaffray EG, McMahon SA, Johnson KA, Navratilova I, Naismith JH, Hay RT. (2011) Mechanism of ubiquitylation by dimeric RING ligase RNF4. Nature Structural and Molecular Biology 18:1052-9

Host: WCB

Ben Lehner - Centre for Genomic Regulation, Spain

WT PhD programme seminar - The genetics of individuals: why would a mutation kill me, but not you?

To what extent is it possible to predict the phenotypic differences among individuals from their completely sequenced genomes?  We use model organisms (yeast, worms and tumours) to understand when you can, and why you cannot, predict the characteristics of individuals from their genome sequences. 

Host: WCB

Mike Lampson - University of Pennsylvania, USA

WT PhD programme seminar - Chromosome segregation in meiosis: violations of Mendel's first law

According to Mendel’s Law of Segregation, alleles segregate away from each other in meiosis, and gametes are equally likely to inherit either allele.  I will discuss two violations of this law.  First, it is well established that the frequency of chromosome segregation errors in female meiosis increases dramatically with age, in both humans and mice.  I will summarize our findings supporting the idea that gradual loss of chromosome cohesion is a major factor contributing to maternal age-related aneuploidy.  Second, chromosome segregation can be balanced, with alleles segregating away from each other, but not random.  A clear example is the segregation of Robertsonian (Rob) translocations in meiosis I.  Rob fusions occur between two acrocentric chromosomes to produce a metacentric chromosome, and their nonrandom segregation is argued to have a major impact on karyotype evolution in mammals.  The mechanisms underlying the nonrandom segregation, also known as meiotic drive, are unknown.  I will show evidence supporting a model in which chromosomes orient preferentially on an asymmetric spindle due to differences in centromere strength.

Host: WCB