Making ends meet: Repair fate mapping illegitimate recombination
This is a hybrid event - with the speaker attending in-person and on Teams 'viewing mode' only.
Abstract:
The repair path of DNA double strand breaks (DSBs) is determined by nuclear process context and the DNA Damage Response (DDR) to suppress chromosome translocations. Although primary DSB repair mechanisms like nonhomologous end joining and homologous recombination are well established, their disrepair and the contribution from alternative DSB repair mechanisms remain to be elucidated, limiting our ability to develop specific and potent cell-based therapies. In this seminar, I will discuss primary and secondary DNA end joining mechanisms, influenced by the DDR, in cycling and quiescent cells from the perspective of genome-wide junction capture studies of physiologic and engineered DSBs. Additionally, from parallel joint capture screens, I will describe several inhibitor classes and gene deficiencies with distinct roles in suppressing V(D)J recombination while separately promoting translocations between Cas9 DSBs. This latter part will highlight a speculative model for how the DDR promotes efficient single DSB rejoining.

Biography:
Dr Richard L. Frock is an Assistant Professor of Radiation and Cancer Biology in the Department of Radiation Oncology at Stanford University. He received his B.A. in Biochemistry at Vassar College and Ph.D. in Biochemistry from the University of Washington studying A-type nuclear laminopathies in striated muscle and lymphocyte development. Richard then completed his postdoctoral training at Harvard Medical School and Boston Children’s Hospital where he made seminal contributions to the development (HTGTS) and improvement (LAM-HTGTS) of a high-throughput chromosome translocation sequencing technology, which has been used extensively to locate recurrent and widespread DNA double-stranded breaks (DSBs) genome-wide in developing lymphocytes and cancer cells and to reveal the collateral damage associated with using engineered endonucleases for genome editing. His group is continuing to evolve this technology, most recently described as reJoin and Translocation sequencing (HTGTS-JoinT-seq), to aid in developing novel therapeutics and to further reveal the underlying biological responses to various sources of DNA damage. Dr Frock is a member of the Stanford Cancer Institute (SCI), Maternal and Childhood Health Research Institute (MCHRI), and the Stanford Bio-X Initiative. He is the recipient of the 1st Annual Career Development Award from the Radiation Research Foundation, a V Scholar for the V Foundation for Cancer Research, and is an American Cancer Society Research Scholar.
Date: 1 April 2025, 11:00
Venue: MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details: WIMM Seminar Room
Speaker: Dr Richard L. Frock (Department of Radiation Oncology, Stanford University)
Organising department: MRC Molecular Haematology Unit
Organisers: Kay Levendale (University of Oxford, MRC Weatherall Institute of Molecular Medicine), Beatriz Hirt-Font (University of Oxford, MRC Weatherall Institute of Molecular Medicine), Emma Butterfield (MRC Weatherall Institute of Molecular Medicine), Fiona Lambert (University of Oxford, MRC Weatherall Institute of Medicine)
Organiser contact email address: mhu-pa@imm.ox.ac.uk
Host: Dr Ross Chapman (University of Oxford)
Part of: Molecular Haematology Unit, WIMM
Booking required?: Not required
Cost: Free
Audience: Members of the University only
Editors: Beatriz Hirt-Font, Kay Levendale