Mechanisms of Recombination: 50 th Anniversary Meeting of the Holliday Model

May 19-23, 2014 Alicante, Spain

Monday, May 19

Afternoon Arrival

17:00 Registration

18:30 Welcome drinks

Keynote lectures:

19:30 – 20:05 Scott Keeney (Memorial Sloan Kettering Cancer Center, US) Meiotic double-strand breaks: starting down the path toward a junction

20:05 – 20:40 David Sherratt (University of Oxford, UK) Recombination in live bacteria

Dinner

Tuesday, May 20

Breakfast

Session 1 Chairperson : Lorraine Symington

09:00 – 09:25 Roland Kanaar (Erasmus MC, The Netherlands) On the behavior of single BRCA2 molecules in live cells and their interaction with RAD51 and DNA damage

09:25 – 09:50 Patrick Sung (, US) Avoidance of rNMP-induced mutations via Srs2-Exo1 dependent mechanism

09:50 – 10:15 Steve Kowalczykowski (University of California, Davis, US) Seeing recombination: one molecule and one step at a time

10:15 – 10:30 Xiaodong Zhang (Imperial College London, UK) Structural characterisations of BRCA2 provide mechanistic insights into Rad51 binding and filament formation during homologous recombination

Break

11:00 – 11:25 Akira Shinohara (Osaka University, Japan) Control of meiotic recombination by Rad51 mediators and DNA helicases

11:25 – 11:50 Hiroshi Iwasaki (Tokyo Institute of Technology, Japan) Activation of Rad51-driven DNA strand exchange reaction by the Swi5-Sfr1 complex

11:50 – 12:15 Wolf-Dietrich Heyer (University of California, Davis, US) Mechanism and regulation of recombinational DNA repair: Rad54 functions as a heteroduplex DNA pump modulated by its DNA substrates and Rad51 during D-loop formation

12:15 – 12:40 Doug Bishop (University of Chicago, US) Recombinosome architecture and homolog bias in meiotic recombination

12:40 – 13:00 Lumír Krej čí (Masaryk University, Czech Republic) DNA damage response proteins as a pharmacological targets

Lunch

15:00 – 16:30 Poster session (odd numbered posters)

Session 2 Chairperson : Stephen West

16:30 – 16:55 John Rouse (University of Dundee, UK) Regulation of DNA repair nucleases in mammals

16:55 – 17:15 Boris Pfander (Max-Planck Institute of Biochemistry, Germany) A cell cycle-regulated Slx4-Dpb11 signalling complex controls the resolution of DNA repair intermediates linked to stalled replication

17:15 – 17:35 Pierre-Henri Gaillard (Marseilles Cancer Research Center, France) SLX4 is a SUMO E3 ligase that impacts on replication stress outcome and genome stability

17:35 – 17:55 Miguel Blanco (London Research Institute, UK) Control of Yen1 activity and localization by Cdk and Cdc14 prevents genome instability

17:55 – 18:15 Petr Cejka (University of Zurich, Switzerland The Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions

Break

18:45 – 19:05 Jeff Sekelsky (University of North Carolina, US) Drosophila GEN is a robust Holliday Junction resolvase that has important functions in vivo

19:05 – 19:25 Dana Branzei (IFOM-IEO Campus, Italy) DNA damage tolerance pathway choice during DNA replication

19:25 – 19:50 Neil Hunter (University of California, Davis, US) Joint molecule metabolism during meiosis

19:50 – 20:15 Michael Lichten (National Cancer Institute, US) Partner choice and product outcome in meiotic recombination

Dinner

Wednesday, May 21

Breakfast

Session 3 Chairperson : Scott Keeney

09:00 – 09:25 Ken Marians (Sloan-Kettering Institute, US) Regression of stalled replication forks

09:25 – 09:50 Lorraine Symington (Columbia University, US) DNA end resection and repair pathway choice

09:50 – 10:15 Rodney Rothstein (Columbia University, US) Increased chromosome mobility facilitates homology search during double-strand break repair

10:15 – 10:30 David Leach (University of Edinburgh, UK) DNA double-strand break repair in E. coli

Break

11:00 – 11:25 Stefan Jentsch (Max Planck Institute, Germany) DNA-protein crosslink repair

11:25 – 11:50 Susan Gasser (Friedrich Miescher Institute, Switzerland) Chromatin dynamics and the homology search

11:50 – 12:15 Monica Colaiacovo (Harvard Medical School, US) Germline maintenance and mechanisms of meiotic recombination in C. elegans

12:15 – 12:40 Luis Aragón (Imperial College London, UK) Smc5/6-dependent regulation of recombination intermediates at damaged replication forks

12:40 – 12:55 Xiaolan Zhao (Memorial Sloan-Kettering Cancer Center, US) Smc5/6- and SUMO-based regulation of recombination intermediate metabolism

12:55 – 13:15 Angelos Constantinou (Institute of Human Genetics, CNRS, France) Replisome surveillance by FANCD2

Lunch

Session 4 Chairperson : Rodney Rothstein

17:00 – 17:25 Andrés Aguilera (CABIMER, Spain) Roles of chromatin, RNA export factors and DSB repair factors in R-loop-mediated genome instability

17:25 – 17:50 James Haber (Brandeis University, US) Frequent template switches during gene conversion and break-induced replication

17:50 – 18:15 Titia de Lange (The Rockefeller University, US) A Holliday Junction binding domain in TRF2 represses PARP1 at mammalian

18:15 – 18:35 Michael Cox (University of Wisconsin - Madison, US) Towards facile genome editing with the RecA-dependent nuclease Ref

Break

19:05 – 19:30 Alain Nicolas (Institut Curie, France) Biological role of G-quadruplexes in replication and genome instability

19:30 – 19:55 Bernard de Massy (Institute of Human Genetics, CNRS, France) The role of PRDM9 in specifying initiation of meiotic recombination in mammals

19:55 – 20:20 Maria Jasin (Sloan-Kettering Institute, US) Meiotic recombination mechanisms and hotspot evolutionary dynamics revealed by mouse tetrad analysis

20:20 – 20:35 Sharon Cantor (University of Massachusetts Medical School, US) A novel mechanism of therapy resistance in BRCA2-mutant cell

Dinner

Thursday, May 22

Breakfast

Session 5 Chairperson : Roland Kanaar

09:00 – 09:25 Agata Smogorzewska (The Rockefeller University, US) RAD51 protects against DNA2-dependent resection during interstrand crosslink repair

09:25 – 09:50 Ian Hickson (Copenhagen University, Denmark) Mechanistic insight into Holliday junction dissolution by the BLM complex

09:50 – 10:15 Jos Jonkers (Netherlands Cancer Institute, The Netherlands) Determinants of therapy response and resistance in mouse models of BRCA1-deficient breast cancer

10:15 – 10:35 Simon Powell (Memorial Sloan Kettering Cancer Center, US) Site-specific DNA replication block in human cells elicits fork cleavage by SLX4 and Mus81

Break

11:05 – 11:30 Simon Boulton (London Research Institute, UK) Rad51 paralogs structurally remodel Rad51 filaments to an active “open” conformation that stimulates strand exchange

11:30 – 11:55 Penny Jeggo (University of Sussex, UK) From non-homologous end-joining to homologous recombination; a regulated switch in repair mechanism usage

11:55 – 12:20 Dale Wigley (Institute of Cancer Research, UK) Structure and mechanism of Chi recognition by AddAB

12:20 – 12:45 John Tainer (Scripps Research Institute, US) MRE11-RAD50 conformations and pathway choice at dsDNA breaks

12:45 – 13:05 Julian Sale (MRC Laboratory of Molecular , UK) Epigenetic instability induced by structured DNA and replication stress

Lunch

15:30 – 17:00 Poster Session (even numbers posters)

Session 6 Chairperson : Agata Smogorzewska

17:00 – 17:25 Virginia Zakian (, US) Genome integrity using yeasts as models

17:25 – 17:50 Marco Foiani (IFOM - F.I.R.C. Inst. of Molecular Oncology Foundation, Italy) Checkpoint-mediated mechanisms controlling chromosome dynamics

17:50 – 18:15 Steve Jackson (University of Cambridge, UK) Assembly and disassembly of protein complexes at sites of DNA damage

18:15 – 18:30 Alessandro Sartori (University of Zurich, Switzerland) FANCD2 recruits CtIP to promote DNA-end resection during the repair of DNA interstrand crosslinks

Break

19:00 – 19:25 Massimo Lopes (University of Zurich, Switzerland) Remodelling of replication intermediates upon replication stress

19:25 – 19:50 John Petrini (Sloan-Kettering Institute, US) Genetic analysis of chromosome break metabolism in eukaryotic cells

Gala Dinner

Friday, May 23

Breakfast

Morning Departure

* Please note, these timings are provisional and are subject to change.