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Mutagenesis
Gordon Research Conference

Mechanisms of Mutagenesis and Genome Alterations

Dates

June 5-10, 2016

Location

PGA Catalunya Business and Convention Centre
Girona, Spain

Organizers

Chair:
Simon Boulton

Vice Chair:
Karlene Cimprich

Meeting Description

The 2016 Mutagenesis GRC will focus on conserved molecular mechanisms of mutagenesis, and how these mechanisms contribute to human diseases such as aging and cancer. Mutations are changes in DNA sequence, which range from single base pair alterations to complex genome rearrangements, which are hallmarks of cancer cells. Metabolic and environmental stresses are major contributors to mutagenesis, and leads to the increased risk of disease, including accelerated aging and age-related diseases such as cancer and neurodegeneration. Moreover, germ line mutations confer inherited diseases, including a wide range of rare diseases and childhood disorders. Conversely, mutagenesis also plays a positive biological role in driving diversity and promoting speciation. Mutagenic mechanisms are also essential for the development of the human immune system, in which the evolution of high-affinity antibodies following exposure to a new antigen depends on the targeted mutation of immunoglobulin genes. The Mutagenesis GRC uniquely addresses the mechanisms and outcomes of mutagenesis in diverse experimental systems. Recent findings by our selected speakers have revealed important new insights into the mechanisms of spontaneous and targeted mutagenesis and the impact on human disease. The conference will highlight new work encompassing a broad range of approaches, from mechanistic studies of mutagenesis, to the recent revolution in whole-genome analysis, to new therapeutic approaches.

Related Meeting

This GRC was held in conjunction with the "Mutagenesis" Gordon Research Seminar (GRS). Refer to the associated GRS program page for more information.

Contributors

Final Meeting Program

Sunday
4:00 pm - 8:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKeynote Session: Focus on Cancer and Aging
Discussion Leader: Simon Boulton (The Francis Crick Institute, United Kingdom)
7:40 pm - 8:25 pmKetan Patel (MRC Laboratory of Molecular Biology, United Kingdom)
"Endogenous DNA Damage in Stem Cells and the Origin of Cancer - A Tale of Two Aldehydes"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 9:20 pmIan Hickson (University of Copenhagen, Denmark)
"Replication-Associated Chromosome Instability as a Driver of Tumorigenesis"
9:20 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmGenome Instability Driven by Transcription/Replication Collisions
Discussion Leader: Sue Jinks-Robertson (Duke University Medical Center, USA)
9:00 am - 9:25 amAndres Aguilera (University of Seville, Spain)
"Role of Chromatin and the DNA Damage Response in Transcription-Associated Genome Instability"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amJesper Svejstrup (The Francis Crick Institute, United Kingdom)
"The Transcription-Related DNA Damage Response"
10:00 am - 10:10 amDiscussion
10:10 am - 10:25 amStephan Hamperl (Stanford University, USA)
"The Orientation of Replication-Transcription Conflicts Affects the Level of R-Loops and Their Consequences on Genomic Stability in Human Cells"
10:25 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:25 amAndre Nussemzweig (National Cancer Institute, NIH, USA)
"Mechanisms of Genome Stability"
11:25 am - 11:35 amDiscussion
11:35 am - 12:00 pmPhilippe Pasero (Institute of Human Genetics, CNRS, France)
"Replication Stress Promotes Inflammation in SAMHD1-Deficient Cells"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmViktoriya Sidorenko (Stony Brook University, USA)
"Human Carcinogen Aristolochic Acid: Mutational Signature and Mechanisms of Bioactivation"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmReplication Stress, Aging and Cancer
Discussion Leader: Thomas Kunkel (National Institute of Environmental Health Sciences, NIH, USA)
6:00 pm - 6:25 pmEric Brown (Perelman School of Medicine, University of Pennsylvania, USA)
"Mapping Replication-Stress Breakpoints"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 6:45 pmMartin Taylor (MRC HGU, Unversity of Edinburgh, United Kingdom)
"The Landscape of Replication-Associated Mutations in the Human and Mouse Germlines"
6:45 pm - 6:50 pmDiscussion
6:50 pm - 7:15 pmOskar Fernandez-Capetillo (Spanish National Cancer Research Center, Spain)
"Mechanisms of Resistance to Anticancer Therapies"
7:15 pm - 7:25 pmDiscussion
7:25 pm - 7:50 pmMark O'Connor (AstraZeneca, United Kingdom)
"Antitumor Activity of the WEE1 Inhibitor AZD1775 as a Monotherapy and in Combination with the PARP Inhibitor Olaparib"
7:50 pm - 8:00 pmDiscussion
8:00 pmDinner
Tuesday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmDNA Repair and Mutagenesis
Discussion Leader: Robert Lahue (National University of Ireland Galway, Ireland)
9:00 am - 9:25 amSusan Rosenberg (Baylor College of Medicine, USA)
"How Bacteria and Cancer Cells Regulate Mutagenesis and Their Ability to Evolve"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amSamuel Wilson (National Institute of Environmental Health Sciences, NIH, USA)
"Observing DNA Polymerase Fidelity by Time-Lapse Crystallography"
10:00 am - 10:10 amDiscussion
10:10 am - 10:25 amScott Lujan (National Institute of Environmental Health Sciences, NIH, USA)
"Polymerase Fidelity and Mismatch Repair Bias Genome Variation and Composition"
10:25 am - 10:30 amDiscussion
10:30 am - 11:00 amCoffee Break
11:00 am - 11:15 amDavid Rueda (Imperial College London, United Kingdom)
"AID-Induced Cotranscriptional Scanning at the Single Molecule Level"
11:15 am - 11:20 amDiscussion
11:20 am - 11:45 amReuben Harris (Howard Hughes Medical Institute, USA)
"Cancer Mutagenesis by APOBEC3 Enzymes"
11:45 am - 11:55 amDiscussion
11:55 am - 12:20 pmJosef Jiricny (University of Zurich, Switzerland)
"The Multifaceted FAN1"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmError-Prone DNA Replication and Repair
Discussion Leader: Roger Woodgate (National Institutes of Health, USA)
6:00 pm - 6:25 pmAnna Malkova (University of Iowa, USA)
"Complex Mutations and Chromosomal Rearrangements Associated with Break-Induced Replication"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 7:00 pmRichard Wood (University of Texas MD Anderson Cancer Center, USA)
"DNA Polymerases and Genome Stability"
7:00 pm - 7:10 pmDiscussion
7:10 pm - 7:35 pmOrlando Scharer (Stony Brook University, USA)
"Replicative and TLS Polymerases in DNA Interstrand Crosslink Repair"
7:35 pm - 7:45 pmDiscussion
7:45 pm - 7:55 pmJacob Jansen (Leiden University Medical Center, The Netherlands)
"A Novel DNA Repair Pathway Correcting Translesion Synthesis Errors"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Wednesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmAging and Cancer-Associated DNA Repair Processes
Discussion Leader: Wei Yang (National Institutes of Health, USA)
9:00 am - 9:25 amSylvie Doublie (University of Vermont, USA)
"When the (3')End Justifies the Means, or How a Family A Polymerase Solves a Major Challenge"
9:25 am - 9:35 amDiscussion
9:35 am - 9:45 amHannah Klein (New York University School of Medicine, USA)
"Asymmetric rNMP Residues in DNA Give Rise to Different Genome Instability Events"
9:45 am - 9:50 amDiscussion
9:50 am - 10:15 amScott Williams (National Institute of Environmental Health Sciences, NIH, USA)
"Mechanisms of Topoisomerase 2 DNA-Protein Crosslink Repair"
10:15 am - 10:25 amDiscussion
10:25 am - 10:40 amJeremy Daniel (Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark)
"SCAI Promotes DNA Double-Strand Break Repair in Distinct Chromosomal Contexts"
10:40 am - 10:45 amDiscussion
10:45 am - 11:15 amCoffee Break
11:15 am - 11:30 amJo Morris (University of Birmingham, United Kingdom)
"The BRCA1-BARD1 Ubiquitin Ligase Activity Counters Chromatin Barriers to DNA Resection"
11:30 am - 11:35 amDiscussion
11:35 am - 12:00 pmKeith Caldecott (University of Sussex, United Kingdom)
"DNA Strand Break Repair and Human Disease"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmNuria Lopez-Bigas (Pompeu Fabra University, Spain)
"Nucleotide Excision Repair Is Impaired by Binding of Transcription Factors to DNA"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmComplex Genome Alterations
Discussion Leader: Ian Hickson (University of Copenhagen, Denmark)
6:00 pm - 6:25 pmAgnel Sfeir (New York University Langone Medical Center, USA)
"mtDNA Replication and Repair: A Modern Take"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 7:00 pmJacqueline Jacobs (Netherlands Cancer Institute, The Netherlands)
"DNA Repair Control at Telomeres and DNA Double-Strand Breaks"
7:00 pm - 7:10 pmDiscussion
7:10 pm - 7:25 pmWojciech Niedzwiedz (University of Oxford, United Kingdom)
"EXD2 – A New Player Joins the DSB Resection Team"
7:25 pm - 7:30 pmDiscussion
7:30 pm - 7:40 pmBjoern Schwer (Boston Children's Hospital, Harvard Medical School, USA)
"Recurrently Breaking Genes in Neural Progenitors: Potential Implications for Neural Function and Disease"
7:40 pm - 7:45 pmDiscussion
7:45 pm - 7:55 pmFrancesco Marchetti (Health Canada, Canada)
"Next Generation Sequencing of Benzo(a)pyrene-Induced lacZ Mutants Identify a Germ Cell-Specific Mutation Spectrum"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Thursday
7:30 am - 8:30 amBreakfast
8:30 am - 9:00 amBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
9:00 am - 12:30 pmDNA Secondary Structures and Repair
Discussion Leader: Nancy Maizels (University of Washington, USA)
9:00 am - 9:25 amCatherine Freudenreich (Tufts University, USA)
"Causes and Consequences of Chromosome Fragility at Expanded CAG Repeats"
9:25 am - 9:35 amDiscussion
9:35 am - 10:00 amChristopher Pearson (The Hospital for Sick Children, Canada)
"ALS, C9orf72 Repeats, and G-Quadruplexes"
10:00 am - 10:10 amDiscussion
10:10 am - 10:45 amCoffee Break
10:45 am - 11:10 amJulian Sale (MRC Laboratory of Molecular Biology, United Kingdom)
"H3.3 Promotes AID-Dependent Mutagenesis"
11:10 am - 11:20 amDiscussion
11:20 am - 11:45 amDaniel Jarosz (Stanford University, USA)
"Protein Homeostasis and Epigenetic Control of Genome Integrity"
11:45 am - 11:55 amDiscussion
11:55 am - 12:20 pmDavid Phillips (King's College London, United Kingdom)
"The Genome as a Record of Environmental Exposure to Carcinogens"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:30 pmFree Time
4:30 pm - 6:00 pmPoster Session
6:00 pm - 8:00 pmMutational Signatures in Aging and Cancer
Discussion Leader: Karlene Cimprich (Stanford University School of Medicine, USA)
6:00 pm - 6:25 pmBen Lehner (ICREA / EMBL-CRG Unit for Research in Systems Biology, Centre for Genomic Regulation, Spain)
"Somatic Mutation Processes in Cancer Genomes"
6:25 pm - 6:35 pmDiscussion
6:35 pm - 7:00 pmSerena Nik-Zainal (Wellcome Trust Sanger Institute, United Kingdom)
"Advances in the Understanding of Signatures of Mutagenesis in Human Somatic Cells"
7:00 pm - 7:10 pmDiscussion
7:10 pm - 7:35 pmCharles Swanton (The Francis Crick Institute, United Kingdom)
"Genome Instability and Cancer Evolution"
7:35 pm - 7:45 pmDiscussion
7:45 pm - 7:55 pmNatalie Saini (National Institute of Environmental Health Sciences, NIH, USA)
"Mutation Loads Accumulated in Genomes of Somatic Cells over the Lifetime of Human Individuals"
7:55 pm - 8:00 pmDiscussion
8:00 pmDinner
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible (in part) by 1R13ES024658-01 from the National Institute of Environmental Health Sciences and the National Cancer Institute (NCI). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
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