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Conference Program
 
Mutagenesis
July 20-25, 2008
Magdalen College
Oxford, United Kingdom
Chair:
Roger Woodgate

Vice Chair:
Nancy Maizels

Mutagenesis plays a central role in our lives. A low level of mutagenesis is advantageous, and ensures the survival of species by promoting evolution. Programmed mutagenesis of immunoglobulin genes promotes diversity and provides a dynamic defense against invading pathogens. However, many human diseases, including most cancers, arise as a consequence of mutations that occur either spontaneously, or are induced by environmental chemical/physical mutagens. Accumulation of oxidative lesions as a result of normal metabolism has been implicated in premature aging and neurodegeneration. Mutagenesis also drives the evolution of virulent bacterial and viral pathogens, allowing them to evolve resistance to therapeutics and thwart the immune response.

The 2008 Mutagenesis Gordon Conference will focus on the molecular mechanisms of mutagenesis that gives rise to genomic instability. In particular, the meeting will enhance our understanding of how mutagenesis occurs in the course of DNA replication and the immune response, and how mutagenesis leads to human genetic disease, cancer, neurodegeneration, and promotes aging. Over the course of four days, morning and evening sessions will focus on: (i) Mutagenesis due to blocked replication and transcription; (ii) Consequences of oxidative stress; (iii) Recombination induced genomic instability; (iv) Physiological mutagenesis in the immune response; (v) Rare human diseases associated with genomic instability, neurodegeneration and premature aging; (vi) Low-fidelity replication and cancer; (vii), Mechanisms of mutagenesis; and (viii) Signaling for repair; a mechanism to avoid excessive mutagenesis.

It is anticipated that the conference will attract a maximum of 150 scientists with diverse interests and experimental approaches and that the informal setting at Magdalen College will foster discussions and the establishment of collaborations that lead to novel scientific discoveries.


Contributors

SUNDAY
2:00 pm - 11:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:45 pmWelcome / Introductory Comments by GRC Site Staff and GRC Chair
7:45 pm - 9:30 pm Keynote Presentations: For better or worse
Session Chairs / Discussion Leaders: Roger Woodgate (NICHD, NIH, USA) & Nancy Maizels (University of Washington, USA)
7:45 pm - 8:25 pmMyron Goodman (University of Southern California, USA)
"Better living through hyper-mutation"
8:25 pm - 8:35 pm Discussion
8:35 pm - 9:15 pmSteve Jackson (University of Cambridge, UK)
"Detection, signalling and repair of DNA double-strand breaks"
9:15 pm - 9:30 pm Discussion
9:30 pm Chair’s opening reception
MONDAY
8:00 am - 9:00 amBreakfast
9:00 am - 12:30 pm Mutagenesis Due to Blocked Replication and Transcription
Session Chair / Discussion Leader: Sue Jinks-Robertson (Duke University, USA)
9:00 am - 9:30 amSue Jinks-Robertson (Duke University, USA)
"Bypassing roadblocks during DNA replication in yeast"
9:30 am - 9:40 am Discussion
9:40 am - 10:05 amRobert Fuchs (CNRS, Marseille, France)
"Polymerase trafficking at the transiently blocked replication fork"
10:05 am - 10:15 am Discussion
10:15 am - 10:30 amJulian Sale (MRC Cambridge, UK)
"The timing and control of translesion synthesis"
10:30 am - 10:35 am Discussion
10:35 am - 11:05 am Coffee Break / Group Photo
11:05 am - 11:30 amGraham Walker (MIT, USA)
"Dealing with DNA problems: Replication Blocks and Template Lesions"
11:30am - 11:40 am Discussion
11:40 am - 11:55 am Dmitry Gordenin (NIEHS, NIH, USA)
"Damage-induced localized hypermutability"
11:55 am - 12:00 pm Discussion
12:00 pm - 12:25 pmAndrés Aguilera (Universidad de Sevilla, Spain)
"Transcription-associated genomic instability in mRNP biogenesis and export mutants"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session I
6:00 pmDinner
7:30 pm - 9:30 pm Consequences of Oxidative Stress
Session Chair / Discussion Leader: Greg Verdine (Harvard University, USA)
7:30 pm - 8:00 pmGreg Verdine (Harvard University, USA)
"Structural and Mechanistic Investigations in DNA Repair"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:25 pmGrigory Dianov (University of Oxford, UK)
"Regulation of base excision repair in response to DNA damage"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:55 pmUeli Hübscher (University of Zurich, Switzerland)
"Faithful translesion synthesis by human DNA polymerases over 8-oxo-guanine"
8:55 pm - 9:00 pm Discussion
9:00 pm - 9:25 pmBruce Demple (Harvard University, USA)
"Preventing Genetic Decay via BER of Oxidative Damage"
9:25 pm - 9:30 pm Discussion
TUESDAY
8:00 am - 9:00 amBreakfast
9:00 am - 12:30 pm Recombination Induced Genomic Instability
Session Chair / Discussion Leader: Penny Jeggo (University of Sussex, UK)
9:00 am - 9:30 amPenny Jeggo (University of Sussex, UK)
"The impact of chromatin structure on double strand break repair and signalling"
9:30 am - 9:40 am Discussion
9:40 am - 10:05 amShunichi Takeda (Kyoto University, Japan)
"Collaboration of BRCA1 and CtIP in cellular tolerance to topoisomerase poisons"
10:05 am - 10:15 am Discussion
10:15 am - 10:30 amKyungjae Myung (NIHGR, NIH, USA)
"Suppression of genomic instability by RAD5-dependent PCNA polyubiquitination in mammalian cells"
10:30 am - 10:35 am Discussion
10:35 am - 11:05 am Coffee Break
11:05 am - 11:30 amJohn Tainer (The Scripps Institute, USA)
"Core Structures and Functions of the Mre1/Rad50/Nbs1 Complex in dsDNA End Binding and dsDNA Break Signaling and Repair"
11:30 am - 11:40 am Discussion
11:40 am - 11:55 amDale Ramsden (University of North Carolina, USA)
"End joining, for better or diverse"
11:55 am - 12:00 pm Discussion
12:00 pm - 12:25 pmSimon Boulton (London Research Institute, UK)
"SPAR1 maintains genome stability through suppression of aberrant recombination events"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session II
6:00 pmDinner
7:30 pm - 9:30 pm Physiological Mutagenesis in the Immune Response
Session Chair / Discussion Leader: Nancy Maizels (University of Washington, USA)
7:30 pm - 8:00 pmNancy Maizels (University of Washington, USA)
"Targeting immunoglobulin gene diversification"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:25 pmHeinz Jacobs (Netherlands Cancer Institute, The Netherlands)
"Role of PCNA modification in somatic hypermutation"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:55 pmPat Gearhart (NIA, NIH, USA)
"Hypermutation in immunoglobulin variable and switch regions"
8:55 pm - 9:00 pm Discussion
9:00 pm - 9:25 pmMichael Neuberger (MRC Cambridge, USA)
"Antibody gene diversification through DNA deamination"
9:25 pm - 9:30 pm Discussion
WEDNESDAY
8:00 am - 9:00 amBreakfast
9:00 am - 12:30 pm Rare Human Diseases Associated with Genomic Instability, Neurodegeneration and Premature Aging
Session Chair / Discussion Leader: Keith Caldecott (University of Sussex, UK)
9:00 am - 9:30 amKeith Caldecott (University of Sussex, UK)
"Mammalian single-strand break repair and human disease"
9:30 am - 9:40 am Discussion
9:40 am - 10:05 amBjörn Schumacher (Erasmus University, The Netherlands)
"DNA damage and the paradoxical link with longevity"
10:05 am - 10:15 am Discussion
10:15 am - 10:30 amSergei Mirkin (Tufts University, USA)
"Large-scale expansions of triplet repeats: mechanisms and implications"
10:35 am - 10:35 am Discussion
10:35 am - 11:05 am Coffee Break
11:05 am - 11:30 amCynthia McMurray (Mayo Clinic, USA)
"MSH2/MSH3: a damage sensor"
11:30am - 11:40 am Discussion
11:40 am - 11:55 amKevin Hiom (MRC Cambridge, UK)
"BRCA1, its interactions and the maintenance of genome stability"
11:55 am - 12:00 pm Discussion
12:00 pm - 12:25 pmWim Vermeulen (Erasmus University, The Netherlands)
"Mouse models of mutant transcription/repair factor TFIIH"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 6:00 pmFree Time / Optional Excursion: Broughton Castle
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 pm Low-fidelity Replication and Cancer
Session Chair / Discussion Leader: Larry Loeb (University of Washington, USA)
7:30 pm - 8:00 pmLarry Loeb (University of Washington, USA)
"The presence and significance of random mutations in human cancers"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:25 pmZvi Livneh (Weizmann Institute, Israel)
"Cancer risk assessment using DNA repair enzymatic activity assays: A tool for lung cancer prevention"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:55 pmFumio Hanaoka (Gakushuin University, Japan)
"In vivo and in vitro studies on DNA polymerase η"
8:55 pm - 9:00 pm Discussion
9:00 pm - 9:25 pmErrol Friedberg (University of Southwestern Texas, USA)
"Lessons Learned From the Polκ Mouse"
9:25 pm - 9:30 pm Discussion
THURSDAY
8:00 am - 9:00 amBreakfast
9:00 am - 12:30 pm Mechanisms of Mutagenesis
Session Chair / Discussion Leader: Tom Kunkel (NIEHS, NIH, USA)
9:00 am - 9:30 amTom Kunkel (NIEHS, NIH, USA)
"Dissecting the fidelity of leading and lagging strand replication fidelity in yeast"
9:30 am - 9:40 am Discussion
9:40 am - 10:05 amFloyd Romesberg (The Scripps Institute, USA)
"Mechanisms of induced mutation in E. coli and S. cerevisiae"
10:05 am - 10:15 am Discussion
10:15 am - 10:30 amPat Foster (Indiana University, USA)
"Stress-induced mutagenesis in E. coli"
10:30 am - 10:35am Discussion
10:35 am - 11:05 am Coffee Break
11:05 am - 11:30 amAlan Lehmann (University of Sussex, UK)
"The role of polκ in nucleotide excision repair"
11:30 am - 11:40 am Discussion
11:40 am - 11:55 amIwona Fijalkowska (Polish Academy of Sciences, Poland)
"Dpb2p, a non catalytic subunit of DNA polymerase epsilon contributes to the fidelity of DNA replication in S. cerevisiae"
11:55 am - 12:00 pm Discussion
12:00 pm - 12:25 pmWei Yang (NIDDK, NIH, USA)
"Translesion DNA synthesis by E. coli pol II"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session III
5:30 pmReception on the Cloisters Lawn
6:00 pmFormal Conference Dinner
7:30 pm - 9:30 pm Signaling for repair: avoiding excessive mutagenesis
Session Chair / Discussion Leader: Joe Jiricny (University of Zurich, Switzerland)
7:30 pm - 8:00 pmJoe Jiricny (University of Zurich, Switzerland)
"Mismatch repair in unusual settings"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:25 pm Joyce Lebbink (Erasmus University, The Netherlands)
"DNA loop formation by the MutS MutL protein complex during early steps of DNA mismatch repair"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:55 pmWei Xiao (University of Saskatchewan, Canada)
"Ubiquitination of DNA clamps: a central signaling for repair and tolerance?"
8:55 pm - 9:00 pm Discussion
9:00 pm - 9:25 pmTom Ellenberger (Washington University, USA)
"Specialization of Mammalian DNA Ligases"
9:25 pm - 9:30 pm Discussion
9:30 pm Chair’s closing reception
FRIDAY
8:00 am - 9:00 amBreakfast
9:00 amDeparture

 
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