
WEBINAR
Only
Genome Integrity Discussion Group October 2021
Monday, October 18, 2021
Webinar
The greater New York metropolitan area is unparalleled in the concentration of world leading research on chromosome biology and function, as well as for research at the interface between chromosome integrity and the dynamics of malignancy. The Genome Integrity Discussion Group capitalizes on this concentration of excellence, providing a forum for interaction between basic- and clinically-oriented research groups working in these fields. These meetings facilitate synergy between labs, and provide a context in which previously unappreciated complementarities can be revealed.
In that spirit, the talks cover a broad range of areas including the DNA damage response and cancer predisposition, DNA replication, transcription, chromatin modification, recombination, cell cycle control, telomeres, chromosome segregation, epigenetic states, as well as the emergence of new technologies relevant to research in genome integrity. Although a primary focus is upon basic mechanisms and processes, these areas are pertinent to cancer and myriad human disease states.
Registration
Genome Integrity Group Members
Monday
October 18, 2021
Welcome Remarks
Topoisomerases I and II Promote Condensin DC Translocation on DNA
Speaker
Adventures in Double-strand Break Repair
Speaker
Mechanism of Loading and Release of the 9-1-1 Checkpoint Clamp by Rad-24 RFC
Speaker
5’ single-stranded/double-stranded DNA junctions are critical for the induction of DNA damage and replication checkpoints by serving as loading sites for the checkpoint clamp, 9-1-1, which mediates the activation of the apical checkpoint kinase, ATRMec1. However, the basis for 9-1-1’s recruitment to 5’ junctions is unclear. Here, we present structures of the yeast checkpoint clamp loader, Rad24-RFC, in complex with 9-1-1 and a 5’ junction as well as a structure of Rad24-RFC in a post-ATP-hydrolysis state. Unexpectedly, 9-1-1 adopts two states in the presence of the loader and DNA, a closed state and an open state in which the ring dilates ~30 Å in a planar fashion. Moreover, Rad24-RFC associates with the junction in the opposite orientation of processivity clamp loaders. Rad24 exclusively recognizes and coordinates the double-stranded region of the DNA, including the 5’ junction, while single-stranded DNA passes into the interior clamp loader chamber. Consequently, contrary to processivity clamps, 9-1-1 is loaded around single-stranded DNA. Upon ATP hydrolysis, Rad24-RFC undergoes large conformational changes that would lead to disengagement of the DNA-loaded 9-1-1 from Rad24-RFC. Together, these structures explain the specific loading of 9-1-1 at 5’ junctions and reveal new principles of the sliding clamp loading mechanism.
Break
ARP2/3- and Resection-coupled Genome Reorganization Facilitates Translocations
Speaker
Pathognomonic Long Molecule Footprints of Homologous Recombination Deficiency
Speaker
Role of the USP1 Deubiquitinase in Mediating Replication Stress
Speaker