BEGIN:VCALENDAR VERSION:2.0 PRODID:talks.ox.ac.uk BEGIN:VEVENT SUMMARY:Chromosome Replication: From Mechanism to Misregulation in Cancer - Prof John Diffley (The Francis Crick Institute) DTSTART;VALUE=DATE-TIME:20190204T130000Z DTEND;VALUE=DATE-TIME:20190204T140000Z UID:https://talks.ox.ac.uk/talks/id/d15b64d0-98fd-492a-ba01-d61846ac00c5/ DESCRIPTION:\nSpeakers:\nProf John Diffley (The Francis Crick Institute) LOCATION:MRC Weatherall Institute of Molecular Medicine (MRC WIMM Seminar Room)\, Headington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/d15b64d0-98fd-492a-ba01-d61846ac00c5/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Chromosome Replication: From Mechanism to Misregulation i n Cancer - Prof John Diffley (The Francis Crick Institute) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:The control of replication fork repair and human disease - Dr Pete r McHugh (University of Oxford\, Weatherall Institute of Molecular Medicin e) DTSTART;VALUE=DATE-TIME:20161208T110000Z DTEND;VALUE=DATE-TIME:20161208T120000Z UID:https://talks.ox.ac.uk/talks/id/f46f7b63-b151-4492-a22e-bc9852fb806c/ DESCRIPTION:Our cellular DNA is constantly being assaulted by reactive met abolites and their by-products. Many of the resulting DNA lesions can be r epaired throughout the cell cycle. However certain forms of damage such as DNA interstrand cross-links (ICLs) and DNA protein crosslinks (DPCs) are selectively recognised and repaired during DNA replication. ICLs and DPCs block DNA replication and if unrepaired\, or misrepaired\, produce devasta ting health conditions. This is exemplified by the inherited syndrome Fanc oni anaemia\, where patients suffer from bone marrow failure\, development al defects and ultimately a massively increased risk of leukaemia and soli d tumours\, often in childhood.\n\nA key effector of the Fanconi anaemia D NA repair pathway is XPF/FANCQ protein. XPF is the active subunit of a dim eric endonuclease (XPF-ERCC1)\, capable of processing damaged replication fork structures. \nDespite the clear link between XPF\, replication-couple d DNA repair and human disease\, very little is known about the mechanism of the recruitment of XPF to damage-arrested forks\, and how XPF interacts with and processes these forks. Here\, I will present our recent advances that include a biochemical reconstitution of replication fork repair\, an d new information on the network or proteins that ensure efficient fork re pair.\n\nSpeakers:\nDr Peter McHugh (University of Oxford\, Weatherall Ins titute of Molecular Medicine) LOCATION:NDM Building (Basement seminar room\, NDM Building (please note: not ORCRB))\, Headington OX3 7FZ TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/f46f7b63-b151-4492-a22e-bc9852fb806c/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:The control of replication fork repair and human disease - Dr Peter McHugh (University of Oxford\, Weatherall Institute of Molecula r Medicine) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:Temporal regulation of genome replication - Professor Conrad Niedu szynski (University of Oxford\, Sir William Dunn School of Pathology) DTSTART;VALUE=DATE-TIME:20160929T123000 DTEND;VALUE=DATE-TIME:20160929T133000 UID:https://talks.ox.ac.uk/talks/id/f3fb3872-eb0f-4220-b0e5-ded212dd4923/ DESCRIPTION:Accurate and complete genome replication is essential for all life. Deregulation of DNA replication can lead to genome instability and i s linked to several human disorders. My research focuses on the cellular r egulation of DNA replication in diverse eukaryotic and prokaryotic cells. Eukaryotic genomes are replicated in a reproducible temporal order. To inv estigate this\, we have developed high-throughput sequencing methods to qu antitatively measure at high resolution the temporal order of genome repli cation. This approach is driving fundamental discoveries about how genomes replicate across the domains of life. For example\, comparing genome repl ication in different species allowed us to discover that replication origi n activity is regulated in cis and that these mechanisms contribute to fai thful chromosome inheritance. Recently\, we have started to investigate th e physiological significance of replication timing. We have identified gen omic features that show an evolutionary conservation in their replication time\, for example\, genes that replicate early in S phase across many spe cies. To test the physiological importance\, we specifically delayed the r eplication time of such genes and discovered that this resulted in reduced gene expression. This is one of the first demonstrations of a physiologic al requirements for regulated replication time and provides a direct link between replication time and gene expression.\nSpeakers:\nProfessor Conrad Nieduszynski (University of Oxford\, Sir William Dunn School of Pathology ) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/f3fb3872-eb0f-4220-b0e5-ded212dd4923/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Temporal regulation of genome replication - Professor Con rad Nieduszynski (University of Oxford\, Sir William Dunn School of Pathol ogy) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:DNA interstrand cross-link and mismatch repair - Dr Jean Gautier ( University of Columbia/Institut Curie) DTSTART;VALUE=DATE-TIME:20160429T113000 DTEND;VALUE=DATE-TIME:20160429T123000 UID:https://talks.ox.ac.uk/talks/id/b4ac83e0-dfa9-4407-b3f5-99afdff6960b/ DESCRIPTION:\nSpeakers:\nDr Jean Gautier (University of Columbia/Institut Curie) LOCATION:Seminar Room TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/b4ac83e0-dfa9-4407-b3f5-99afdff6960b/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:DNA interstrand cross-link and mismatch repair - Dr Jean Gautier (University of Columbia/Institut Curie) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:DNA repair\, NAD+ and mitophagy in neurodegeneration and ageing - Dr Evandro Fang (National Institutes on Aging\, Bethesda\, MD\, USA) DTSTART;VALUE=DATE-TIME:20160405T130000 DTEND;VALUE=DATE-TIME:20160405T140000 UID:https://talks.ox.ac.uk/talks/id/6223750d-1fc2-4fef-b9f6-0abc8ff0872f/ DESCRIPTION:Ageing is emerging as a universal problem bringing formidable socioeconomic challenges. Studies on the mechanisms of ageing will facilit ate our understanding of the process and will generate potential preventiv e strategies. Since no single ageing theory can satisfactorily explain all aspects of the ageing process\, an integration of multiple theories on ag eing is favored. The speaker will describe his latest studies on how two c lassical ageing hypotheses\, persistent DNA damage and mitochondrial dysfu nction\, converge to explain premature ageing symptoms and contribute to n eurological phenotypes in a series of ageing laboratory models. Emerging e vidence suggests a critical role for DNA damage signalling from the nucleu s to mitochondria (NM signalling) in regulating mitochondrial function and ageing. The interconnected roles of DNA damage\, NAD+\, and mitophagy wil l be explored in relation to ageing and neurodegenerative diseases\, espec ially Alzheimer’s disease.\nSpeakers:\nDr Evandro Fang (National Institu tes on Aging\, Bethesda\, MD\, USA) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/6223750d-1fc2-4fef-b9f6-0abc8ff0872f/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:DNA repair\, NAD+ and mitophagy in neurodegeneration and ageing - Dr Evandro Fang (National Institutes on Aging\, Bethesda\, MD\, U SA) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:Chromosome DNA strand break repair and genetic disease - Keith Cal decott (Deputy Director\, Genome Damage and Stability Centre\, University of Sussex ) DTSTART;VALUE=DATE-TIME:20160704T130000 DTEND;VALUE=DATE-TIME:20160704T140000 UID:https://talks.ox.ac.uk/talks/id/3eaa4696-ca01-41bd-a380-0b2a06484d1e/ DESCRIPTION:\nSpeakers:\nKeith Caldecott (Deputy Director\, Genome Damage and Stability Centre\, University of Sussex ) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/3eaa4696-ca01-41bd-a380-0b2a06484d1e/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Chromosome DNA strand break repair and genetic disease - Keith Caldecott (Deputy Director\, Genome Damage and Stability Centre\, Un iversity of Sussex ) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:How does the Fanconi pathway promote unhooking of DNA interstrand crosslinks? - Dr Puck Knipscheer (Hubrecht Institute\, Utrecht\, Netherlan ds) DTSTART;VALUE=DATE-TIME:20160324T123000Z DTEND;VALUE=DATE-TIME:20160324T133000Z UID:https://talks.ox.ac.uk/talks/id/6b41a8f9-05ec-41e5-90e1-61f77b8af9c7/ DESCRIPTION:DNA interstrand cross-links (ICLs) are highly toxic DNA lesion s as they prevent DNA strand separation. ICL repair requires several class es of repair enzymes including translesion DNA polymerases\, structure-spe cific endonucleases\, recombinases\, and Fanconi anemia (FA) proteins. Mut ation in any one of the 16 currently known FA genes leads to the cancer pr edisposition disorder Fanconi anemia. However\, it is still largely unclea r how the FA proteins and the other repair factors collaborate to repair I CLs.\nWe study the molecular mechanism of ICL repair using a Xenopus egg e xtract-based system that recapitulates replication-dependent ICL repair in vitro. Previously we have shown that activation of the FA pathway by ubiq uitylation of the FANCI-FANCD2 (ID) complex is important for a specific st ep in ICL repair\, namely the incisions that unhook the lesion from one of the DNA strands. We next demonstrated that binding of this activated ID c omplex to the crosslink promotes the recruitment of the incision-complex\, composed of the adapter protein SLX4 and the structure specific endonucle ase XPF-ERCC1. Both XPF and SLX4 have recently been identified as FA genes highlighting their importance in ICL repair. Although ICL unhooking appea rs to be a major function of the FA pathway the biochemical details of thi s process are still unclear. I will present our latest findings regarding the role of XPF-ERCC1 and SLX4 in ICL repair.\n\nSpeakers:\nDr Puck Knipsc heer (Hubrecht Institute\, Utrecht\, Netherlands) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/6b41a8f9-05ec-41e5-90e1-61f77b8af9c7/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:How does the Fanconi pathway promote unhooking of DNA int erstrand crosslinks? - Dr Puck Knipscheer (Hubrecht Institute\, Utrecht\, Netherlands) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:Exploiting replication stress to target histone H3K36me3-deficient cancers - Dr Tim Humphrey (University of Oxford\, Old Road Campus Researc h Building) DTSTART;VALUE=DATE-TIME:20151020T110000 DTEND;VALUE=DATE-TIME:20151020T120000 UID:https://talks.ox.ac.uk/talks/id/c6a0e157-19ec-4492-85e0-fd07aefdb387/ DESCRIPTION:\nSpeakers:\nDr Tim Humphrey (University of Oxford\, Old Road Campus Research Building) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/c6a0e157-19ec-4492-85e0-fd07aefdb387/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Exploiting replication stress to target histone H3K36me3- deficient cancers - Dr Tim Humphrey (University of Oxford\, Old Road Campu s Research Building) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:Forward genetic screens in haploid mammalian cells: looking beyond CRISPR/Cas9 - Dr Josep Forment (University of Cambridge) DTSTART;VALUE=DATE-TIME:20150716T143000 DTEND;VALUE=DATE-TIME:20150716T153000 UID:https://talks.ox.ac.uk/talks/id/e46e3212-fae7-41c8-97b1-18affe08f3aa/ DESCRIPTION:\nSpeakers:\nDr Josep Forment (University of Cambridge) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/e46e3212-fae7-41c8-97b1-18affe08f3aa/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Forward genetic screens in haploid mammalian cells: looki ng beyond CRISPR/Cas9 - Dr Josep Forment (University of Cambridge) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:Forward genetic screens in haploid mammalian stem cells: looking b eyond CRISPR/Cas9 - Dr Josep Forment (University of Cambridge) DTSTART;VALUE=DATE-TIME:20150716T143000 DTEND;VALUE=DATE-TIME:20150716T153000 UID:https://talks.ox.ac.uk/talks/id/bb2ab4f1-c624-4400-82ea-30ff7ad37ea7/ DESCRIPTION:Recent adaptation of the CRISPR/Cas9 bacterial system to facil itate manipulation of mammalian genomes has provided a real breakthrough f or genome editing applications. Development of whole-genome CRISPR librari es with the aim of generating gene knockouts for every single coding seque nce has allowed forward genetic screening in mammalian cells with unpreced ented efficiency and versatility. CRISPR/Cas9 approaches\, however\, rely on phenotypes associated with loss-of-function mutations. Single-nucleotid e variations (SNVs)\, on the other hand\, have the potential to uncover no t only loss-of-function phenotypes (by generating nonsense mutations\, for example) but also gain-of-function phenotypes through missense mutations. In addition\, they produce valuable information regarding functionally im portant domains of the affected gene product\, as SNVs causative of a part icular phenotype tend to cluster around specific regions of the amino acid sequence of the encoded protein. SNV-based approaches in mammalian cells\ , however\, have been hindered by the diploid nature of their genomes\, a fact that complicates the establishment of straightforward genotype-to-phe notype correlations. In this talk I will discuss how we apply CRISPR/Cas9 genetic screening to further understand the DNA-damage response in mouse e mbryonic stem cells (mESCs)\, and I will also introduce the use of haploid mESCs to perform SNV-based forward genetic screens.\nSpeakers:\nDr Josep Forment (University of Cambridge) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/bb2ab4f1-c624-4400-82ea-30ff7ad37ea7/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Forward genetic screens in haploid mammalian stem cells: looking beyond CRISPR/Cas9 - Dr Josep Forment (University of Cambridge) TRIGGER:-PT1H END:VALARM END:VEVENT BEGIN:VEVENT SUMMARY:DNA double-strand break repair in immunity and tumour suppression - Dr Ross Chapman (University of Oxford) DTSTART;VALUE=DATE-TIME:20150430T123000 DTEND;VALUE=DATE-TIME:20150430T133000 UID:https://talks.ox.ac.uk/talks/id/c4f4b207-1817-47fa-b4a4-534915313f51/ DESCRIPTION:\nSpeakers:\nDr Ross Chapman (University of Oxford) LOCATION:MRC Weatherall Institute of Molecular Medicine (Seminar Room)\, H eadington OX3 9DS TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/c4f4b207-1817-47fa-b4a4-534915313f51/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:DNA double-strand break repair in immunity and tumour sup pression - Dr Ross Chapman (University of Oxford) TRIGGER:-PT1H END:VALARM END:VEVENT END:VCALENDAR