BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation.
Authors:Isono M, Niimi A, Oike T, Hagiwara Y, Sato H, Sekine R, Yoshida Y, Isobe SY, Obuse C, Nishi R, Petricci E, Nakada S, Nakano T, Shibata A
Journal:Cell Rep
PubMed ID:28076794
'BRCA1 promotes homologous recombination (HR) by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resection by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 ... More
DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis.
Authors:Milani M, Byrne DP, Greaves G, Butterworth M, Cohen GM, Eyers PA, Varadarajan S
Journal:Cell Death Dis
PubMed ID:28079887
'The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. ... More
Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA.
Authors:Liang X, Potter J, Kumar S, Ravinder N, Chesnut JD
Journal:J Biotechnol
PubMed ID:27845164
'While CRISPR-based gene knock out in mammalian cells has proven to be very efficient, precise insertion of genetic elements via the cellular homology directed repair (HDR) pathway remains a rate-limiting step to seamless genome editing. Under the conditions described here, we achieved up to 56% targeted integration efficiency with up ... More
Development of a Bacillus subtilis cell-free transcription-translation system for prototyping regulatory elements.
'Cell-free transcription-translation systems were originally applied towards in vitro protein production. More recently, synthetic biology is enabling these systems to be used within a systematic design context for prototyping DNA regulatory elements, genetic logic circuits and biosynthetic pathways. The Gram-positive soil bacterium, Bacillus subtilis, is an established model organism of ... More
Evaluation of Receptor-Ligand Mechanisms of Dual-Targeted Particles to an Inflamed Endothelium.
Authors:Fromen CA, Fish MB, Zimmerman A, Adili R, Holinstat M, Eniola-Adefeso O
Journal:Bioeng Transl Med
PubMed ID:28066821
'Vascular-targeted carriers (VTCs) are designed as leukocyte mimics, decorated with ligands that target leukocyte adhesion molecules (LAMs) and facilitate adhesion to diseased endothelium. VTCs require different design considerations than other targeted particle therapies; adhesion of VTCs in regions with dynamic blood flow requires multiple ligand-receptor (LR) pairs that provide particle ... More