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Conference Program
 
Mutagenesis
A Delicate Balance: Cellular Mutation Pathways in Genetic Stability and Disease
August 19-24, 2012
Salve Regina University
Newport, RI
Chair:
Bruce Demple

Vice Chair:
Robert Lahue

The delicate balance among cellular pathways that control mutagenic changes in DNA will be the focus of the 2012 Mutagenesis Gordon Research Conference. Mutagenesis is essential for evolution, while genetic stability maintains cellular functions in all organisms from microbes to metazoans. Different systems handle DNA lesions at various times of the cell cycle and in different places within the nucleus, and inappropriate actions can lead to mutations. While mutation in humans is closely linked to disease, notably cancers, mutational systems can also be beneficial. The conference will highlight topics of beneficial mutagenesis, including full establishment of the immune system, cell survival mechanisms, and evolution and adaptation in microbial systems. Equal prominence will be given to detrimental mutation processes, especially those involved in driving cancer, neurological diseases, premature aging, and other threats to human health. Provisional session titles include Branching Pathways in Mutagenesis; Oxidative Stress and Endogenous DNA Damage; DNA Maintenance Pathways; Recombination, Good and Bad; Problematic DNA Structures; Localized Mutagenesis; Hypermutation in the Microbial World; and Mutation and Disease. The sessions will be based on presentations by leading scientists, and the program will also include short talks by younger investigators selected from submitted abstracts. The key goals of the conference are to bring together people representing diverse approaches, to stimulate presentation and discussion of new ideas, to catalyze new collaborations, and to encourage full involvement by those new to the field. The spectacular setting at Salve Regina University in Newport, Rhode Island is an added benefit that ensures a productive and enjoyable conference.


Contributors

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKEYNOTE PRESENTATIONS
Discussion Leader: Bruce Demple (Stony Brook University School of Medicine, Stony Brook, NY)
7:40 pm - 8:25 pmThomas A. Kunkel (NIEHS, Research Triangle Park, NC)
"Determinants of leading and lagging strand DNA replication fidelity"
8:25 pm - 8:35 pmDiscussion
8:35 pm - 9:20 pmTitia de Lange (Rockefeller University, New York, NY)
"How telomeres solve the end-protection problem"
9:20 pm - 9:30 pmDiscussion
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmBRANCHING PATHWAYS IN MUTAGENESIS
Discussion Leader: Robert P.P. Fuchs (CNRS Genome Instability and Carcinogenesis Unit, Marseille, France)
9:00 am - 9:30 amRobert P.P. Fuchs (CNRS Genome Instability and Carcinogenesis Unit, Marseille, France)
"The role of dNTP pool size in spontaneous and induced mutagenesis in E. coli"
9:30 am - 9:40 amDiscussion
9:40 am - 10:05 amRoger Woodgate (NICHHD, NIH, Bethesda, MD)
"Characterization of novel E. coli polV mutants"
10:05 am - 10:15 amDiscussion
10:15 am - 10:45 amGroup Photo / Coffee Break
10:45 am - 11:10 amHelle Ulrich (London Research Institute/CRUK, South Mimms, UK)
"Mechanism of ubiquitin-dependent DNA damage bypass"
11:10 am - 11:20 amDiscussion
11:20 am - 11:33 amJoseph Loparo (Harvard Medical School, Boston, MA)
"Concentration-dependent interactions with the sliding clamp serve as a switch for regulating translesion polymerase exchange"
11:33 am - 11:38 amDiscussion
11:38 am - 11:51 amMatthew Northam (University of Nebraska Medical Center, Omaha, NE)
"Yeast DNA polymerases zeta and Rev1 aid in the bypass of non-canonical secondary structures in DNA"
11:51 am - 11:55 amDiscussion
11:55 am - 12:20 pmJosef Jiricny (University of Zurich, Zurich, Switzerland)
"The mismatch repair interactome"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmOXIDATIVE STRESS AND ENDOGENOUS DNA DAMAGE
Discussion Leader: Sarah Delaney (Brown University, Providence, RI))
7:30 pm - 7:55 pmSarah Delaney (Brown University, Providence, RI)
"Contribution of oxidatively damaged DNA to triplet repeat expansion"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:30 pmPaul Doetsch (Emory University School of Medicine, Atlanta, GA)
"Transcriptional mutagenesis and oxidative DNA damage"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 8:50 pmAlain Nepveu (McGill University, Montreal, Canada)
"Ras-Induced Oxidative Damage and Recruitment of REV1 to Transcribed Regions"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:20 pmDavid M. Wilson (National Institute on Aging, Baltimore, MD)
"Defects in the repair of endogenous DNA damage"
9:20 pm - 9:30 pmDiscussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDNA MAINTENANCE PATHWAYS
Discussion Leader: Peter Burgers (Washington University School of Medicine, St. Louis, MO)
9:00 am - 9:30 amPeter Burgers (Washington University School of Medicine, St. Louis, MO)
"Control of damage-induced mutagenesis through Rev1"
9:30 am - 9:40 amDiscussion
9:40 am - 10:05 amRobert Sobol (Univ. of Pittsburgh School of Medicine, Pittsburgh, PA)
"Exploring the Polβ/XRCC1 interface and the regulation of base excision repair"
10:05 am - 10:15 amDiscussion
10:15 am - 10:45 amCoffee Break
10:45 am - 11:10 amJohn Tainer (Scripps Research Institute, La Jolla, CA)
"XPD, FEN1 and MRN conformations and complexes: Envisioning DNA repair interfaces with transcription and replication"
11:10 am - 11:20 amDiscussion
11:20 am - 11:33 amCeline Walmacq (National Cancer Institute, NIH, Bethesda, MD)
"Mechanism of Translesion Transcription by RNA Polymerase II and Its Role in Cellular Resistance to DNA Damage"
11:33 am - 11:38 amDiscussion
11:38 am - 11:51 amBenu Das (National Cancer Institute, NIH, Bethesda, MD)
"PARP1 is a critical cofactor for Tyrosyl-DNA phosphodiesterase (TDP1) repair function"
11:51 am - 11:55 amDiscussion
11:55 am - 12:20 pmMaria Falkenberg Gustafsson (University of Gothenburg, Sweden)
"Linking transcription to DNA replication in human mitochondria"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmRECOMBINATIONAL PATHWAYS, GOOD AND BAD
Discussion Leader: Maria Jasin (MSKCC, New York, NY)
7:30 pm - 7:55 pmMaria Jasin (MSKCC, New York, NY)
"Protecting the genome through homologous recombination"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:30 pmDale Ramsden (University of North Carolina, Chapel Hill, NC)
"Assessing the fidelity of the 'error-prone' double strand break repair pathway"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 8:50 pmMitch McVey (Tufts University, Medford, MA)
"Multiple translesion polymerases are involved in mutagenic DNA double-strand break repair"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:20 pmSimon Boulton (London Research Institute/CRUK, South Mimms, UK)
"Molecular Basis of T-loop disassembly and suppression of telomere fragility by RTEL1"
9:20 pm - 9:30 pmDiscussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmPROBLEMATIC DNA STRUCTURES
Discussion Leader: Robert Lahue (National University of Ireland, Galway)
9:00 am - 9:30 amRobert Lahue (National University of Ireland, Galway)
"Genes that promote trinucleotide repeat expansions"
9:30 am - 9:40 amDiscussion
9:40 am - 10:05 amNancy Maizels (University of Washington School of Medicine, Seattle, WA)
"Solving the problems posed by DNA structures"
10:05 am - 10:15 amDiscussion
10:15 am - 10:45 amCoffee Break
10:45 am - 10:58 amJennifer Surtees (SUNY Buffalo School of Medicine, Buffalo, NY)
"Msh2-Msh3 interferes with Okazaki fragment processing to promote trinucleotide repeat expansions"
10:58 am - 11:02 amDiscussion
11:02 am - 11:15 amIvaylo Ivanov (Georgia State University, Atlanta, GA)
"Repair complexes of FEN1, DNA and Rad9-Hus1-Rad1 are distinguished from their PCNA counterparts by functionally important stability"
11:15 am - 11:20 amDiscussion
11:20 am - 11:45 amCatherine Freudenreich (Tufts University, Medford, MA)
"Factors governing repair fidelity within CAG trinucleotide repeats"
11:45 am - 11:55 amDiscussion
11:55 am - 12:08 pmSabrina Mansilla (Insituto Leloir Fundación, Buenos Aires, Argentina)
"A failure to downregulate the negative regulator of TLS, p21, upon UV irradiation generates damaged-DNA replication defects and triggers apoptosis and genomic instability"
12:08 pm - 12:13 pmDiscussion
12:13 pm - 12:26 pmCatherine Potenski (NYU School of Medicine, New York, NY)
"Role of the RNaseH2 complex and the Srs2 DNA helicase in maintaining genome stability and mutation avoidance"
12:26 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair
7:30 pm - 9:30 pmHYPERMUTATION IN THE MICROBIAL WORLD
Discussion Leader: Jeffrey H. Miller (UCLA, Los Angeles, CA)
7:30 pm - 7:55 pmJeffrey H. Miller (UCLA, Los Angeles, CA)
"The origin of mutations in the pools of nucleoside diphosphates generated by the degradation of RNA"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:30 pmSue Lovett (Brandeis University, Waltham, MA)
"DNA structure-associated mutational hotspots"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 8:50 pmFrancesca Storici (Georgia Institute of Technology, Atlanta, GA)
"Mechanisms of RNA-driven DNA damage and repair"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:20 pmSue Jinks-Robertson (Duke University Medical Center, Raleigh, NC)
"Topoisomerase I and genome stability in yeast"
9:20 pm - 9:30 pmDiscussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmTISSUE-SPECIFIC AND AGING-RELATED MUTAGENESIS
Discussion Leader: Christi Walter (UT Health Sciences Center, San Antonio, TX)
9:00 am - 9:30 amChristi Walter (UT Health Sciences Center, San Antonio, TX)
"The paternal age effect - A disruption of genetic integrity mechanisms in the male germline"
9:30 am - 9:40 amDiscussion
9:40 am - 10:05 amMyron F. Goodman (University of Southern California, Los Angeles, CA)
"A drunkard's walk approach to generate mutational diversity - ssDNA scanning by AID & APOBEC C-deaminases"
10:05 am - 10:15 amDiscussion
10:15 am - 10:45 amCoffee Break
10:45 am - 11:10 amDiane Cabelof (Wayne State University, Detroit, MI)
"Accumulation of somatic copy number variants with age"
11:10 am - 11:20 amDiscussion
11:20 am - 11:33 amSonia Franco (Johns Hopkins University, Baltimore, MD)
"PARP1 and DNA-PKcs synergize to suppress p53 mutation and telomere fusions during T lineage lymphomagenesis"
11:33 am - 11:38 amDiscussion
11:38 am - 11:51 amFederica Polato (National Cancer Institute, NIH, Bethesda, MD)
"Understanding the role of CtIP in DSB repair"
11:51 am - 11:55 amDiscussion
11:55 am - 12:20 pmKeith Caldecott (University of Sussex, Falmer, UK)
"New insights into DNA strand break repair"
12:20 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmMUTATION AND DISEASE
Discussion Leader: Lawrence A. Loeb (University of Washington School of Medicine)
7:30 pm - 7:55 pmLawrence A. Loeb (University of Washington School of Medicine, Seattle, WA)
"Mutational heterogeneity in human cancers: Origin and consequences"
7:55 pm - 8:05 pmDiscussion
8:05 pm - 8:30 pmNiels de Wind (Leiden University Medical Centre, Leiden, Netherlands)
"A mismatch repair pathway that regulates responses to photolesions by controlling translesion synthesis"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 8:50 pmReuben Harris (University of Minnesota, Minneapolis, MN)
"Enzyme Catalyzed DNA Deamination in Multiple Human Cancers"
8:50 pm - 8:55 pmDiscussion
8:55 pm - 9:20 pmKristin Eckert (Pennsylvania State University, State College, PA)
"Microsatellite stability in the human genome: When interrupting is a good thing"
9:20 pm - 9:30 pmDiscussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible (in part) by 1R13CA171305-01 from the National Cancer Institute. 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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