A5009417663- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- PARP inhibition in cancer therapy
- Microtubule and mitosis dynamics
- Pancreatitis Pathology and Treatment
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- RNA modifications and cancer
Memorial Sloan Kettering Cancer Center
2021-2022
Cornell University
2022
Weill Cornell Medicine
2022
The DNA sliding clamp proliferating cell nuclear antigen (PCNA) is an essential co-factor for many eukaryotic metabolic enzymes. PCNA loaded around by the ATP-dependent loader replication factor C (RFC), which acts at single-stranded (ss)/double-stranded (dsDNA) junctions harboring a recessed 3’ end (3’ ss/dsDNA junctions) and nicks. To illuminate loading mechanism we have investigated structure of RFC:PCNA bound to ATPγS or nicked using cryogenic electron microscopy. Unexpectedly, observe...
Abstract 5’ single-stranded/double-stranded DNA serve as loading sites for the checkpoint clamp, 9-1-1, which mediates activation of apical kinase, ATR Mec1 . However, basis 9-1-1’s recruitment to junctions is unclear. Here, we present structures yeast clamp loader, Rad24-RFC, in complex with 9-1-1 and a junction post-ATP-hydrolysis state. Unexpectedly, adopts both closed planar open states presence Rad24-RFC DNA. Moreover, associates opposite orientation processivity loaders Rad24...
Abstract The DNA sliding clamp proliferating cell nuclear antigen (PCNA) is an essential co-factor for many eukaryotic metabolic enzymes. PCNA loaded around by the ATP-dependent loader replication factor C (RFC), which acts at single-stranded/double-stranded junctions harboring a recessed 3’ end (3’ ss/dsDNA junctions) and nicks. To illuminate loading mechanism we have investigated structure of RFC:PCNA bound to ATPγS or nicked using cryogenic electron microscopy. Unexpectedly, observe open...