Richard L. Frock
Harvard University
Molecular biologyLMNAGeneticsDNABiology
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Publications 25
#1Xiaoyu Chen (LUMC: Leiden University Medical Center)H-Index: 7
#2Francesca Tasca (LUMC: Leiden University Medical Center)
Last. Manuel A. F. V. Gonçalves (LUMC: Leiden University Medical Center)H-Index: 23
view all 11 authors...
#1Richard L. FrockH-Index: 14
#2Vipul KumarH-Index: 4
Last. Frederick W. AltH-Index: 157
view all 8 authors...
#1Jacob V. Layer (Harvard University)H-Index: 3
#2J. Patrick Cleary (Harvard University)H-Index: 2
Last. Tovah A. Day (Harvard University)H-Index: 7
view all 18 authors...
Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. ...
2 CitationsSource
#1Nicholas A. Willis (Harvard University)H-Index: 12
#2Richard L. Frock (HHMI: Howard Hughes Medical Institute)H-Index: 14
Last. Ralph Scully (Harvard University)H-Index: 38
view all 10 authors...
BRCA1, but not BRCA2, suppresses the formation of tandem duplications at stalled replication forks in primary mammalian cells.
21 CitationsSource
#1Bruna S. Paulsen (Harvard University)H-Index: 2
#2Pankaj K. Mandal (Harvard University)H-Index: 20
Last. Derrick J. RossiH-Index: 52
view all 14 authors...
Gene disruption by clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) is highly efficient and relies on the error-prone non-homologous end-joining pathway. Conversely, precise gene editing requires homology-directed repair (HDR), which occurs at a lower frequency than non-homologous end-joining in mammalian cells. Here, by testing whether manipulation of DNA repair factors improves HDR efficacy, we show that transient ectopic co-expression of RA...
11 CitationsSource
#1Fabio Vanoli (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
#2Shuhei Ito (Kyushu University)
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 6 authors...
Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA damage response pathways to be targeted by specific inhibitors for clinical benefit. Tumors with defects in homologous recombination (HR) are hypersensitive to PARP inhibitors (PARPi), and early phase clinical trials have been promising in patients with advanced BRCA1 and BRCA2-associated breast, ovary and prostate cancer. Unlike HR-defective cells, HR-proficient cells manifest low cytotoxicity when exposed to P...
#1Kumar (Harvard University)H-Index: 1
#2Frederick W. Alt (Harvard University)H-Index: 157
Last. Richard L. Frock (Harvard University)H-Index: 14
view all 3 authors...
Abstract Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway. Core C-NHEJ factors, such as XRCC4, are required for joining DSB intermediates of the G1 phase-specific V(D)J recombination reaction in progenitor lymphocytes. Core factors also contribute to joining DSBs in cycling mature B-lineage cells, including DSBs generated during antibody class switch recombination (CSR) and DSBs generated by ionizing radiation. The XRCC4-like-factor (...
34 CitationsSource
#1Lijuan Zhao (HHMI: Howard Hughes Medical Institute)H-Index: 5
#2Richard L. Frock (HHMI: Howard Hughes Medical Institute)H-Index: 14
Last. Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
view all 7 authors...
T cell antigen receptor δ ( Tcrd ) variable region exons are assembled by RAG-initiated V(D)J recombination events in developing γδ thymocytes. Here, we use linear amplification–mediated high-throughput genome-wide translocation sequencing (LAM-HTGTS) to map hundreds of thousands of RAG-initiated Tcrd D segment ( Trdd1 and Trdd2 ) rearrangements in CD4−CD8− double-negative thymocyte progenitors differentiated in vitro from bone marrow–derived hematopoietic stem cells. We find that Trdd2 joins di...
17 CitationsSource
#1Pankaj K. MandalH-Index: 20
#2Bruna S. PaulsenH-Index: 2
Last. Derrick J. RossiH-Index: 52
view all 8 authors...
CRISPR/Cas9 system allows efficient gene ablation through error-prone non-homologous end joining DNA repair. However, very low efficiency of homology-directed DNA repair (HDR) is the bottleneck in correcting genetic mutations of clinical relevance. Here we report that transient manipulation of DNA damage repair pathways increases the HDR frequency by 3-5 fold. Furthermore, we show that this approach is applicable to introduce precise genetic modifications at many genetic loci in multiple cell-ty...
#1Jiazhi HuH-Index: 12
#2Robin M. MeyersH-Index: 17
Last. Richard L. FrockH-Index: 14
view all 6 authors...
This protocol describes a genome-wide method to detect and to quantify DNA double-stranded breaks (DSBs). The approach is applicable to endogenous DSBs, but it can also be used to characterize the activity of engineered nucleases, including Cas9.
54 CitationsSource