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SUMMARY:Perutz LMB Seminar Series: How our chromosomes are replicated - Jo
 hn Diffley\, Associate Research Director\, the Francis Crick Institute\, L
 ondon\, UK
DTSTART:20200226T110000Z
DTEND:20200226T120000Z
UID:TALK134005@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The eukaryotic cell cycle coordinates the accurate duplication
  and segregation of the genome during proliferation.  The large genomes of
  eukaryotic cells are replicated from multiple replication origins during 
 S phase.  These origins are not activated synchronously at the beginning o
 f S phase\, but instead fire throughout S phase according to a pre-determi
 ned\, cell type specific program.  In addition to duplication of genomic D
 NA\, all of the protein components of chromosomes must be duplicated and p
 laced in the correct locations during S phase so gene expression patterns 
 can be maintained.  Replication must also be coordinated with many nuclear
  processes including sister chromatid cohesion\, replication checkpoint ac
 tivation\, postreplication repair and chromatin assembly.\nEnsuring that e
 ach origin is efficiently activated once and only once during each S phase
  is crucial for maintaining the integrity of the genome.  This is achieved
  by a two-step mechanism.  The first step\, known as licensing\, involves 
 the loading of the Mcm2-7 proteins into pre-replicative complexes (pre-RCs
 ) at origins. In the second step\, the MCM helicase is activated by a larg
 e set of ‘firing factors’. These two steps are differentially regulate
 d by cyclin dependent kinase (CDK): licensing is inhibited by CDK\, whilst
  firing requires CDK. As a consequence\, licensing can only happen during 
 G1 phase\, when CDK activity is low\, and origin firing cannot occur durin
 g G1 phase.  Misregulation of this system can generate chromosome rearrang
 ements which may contribute to genome instability in cancer.\nWe have desc
 ribed the reconstitution of yeast DNA replication with purified proteins. 
  I will present recent results using this system to study the mechanism of
  DNA replication and the processes associated with it\, ensuring accurate 
 chromosome duplication. \n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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