Zinc Coordination Is Required for and Regulates Transcription Activation by Epstein-Barr Nuclear Antigen 1

Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO2). Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO2 and redox potential

On the design of experiments for the study of relativistic nonlinear optics in the limit of single-cycle pulse duration and single-wavelength spot size

We propose a set of experiments with the aim of studying for the first time relativistic nonlinear optics in the fundamental limits of single-cycle pulse duration and single-wavelength spot size. The laser system that makes this work possible is now operating at the Center for Ultrafast Optical Science at the University of Michigan. Its high repetition rate (1 kHz) will make it possible to perform a detailed investigation of relativistic effects in this novel regime. This study has the potential to make the field of relativistic optics accessible to a wider community and to open the door for real-world applications of relativistic optics, such as electron/ion acceleration and neutron and positron production.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45803/1/11452_2005_Article_253.pd

Relativistic Laser-Matter Interaction and Relativistic Laboratory Astrophysics

The paper is devoted to the prospects of using the laser radiation interaction with plasmas in the laboratory relativistic astrophysics context. We discuss the dimensionless parameters characterizing the processes in the laser and astrophysical plasmas and emphasize a similarity between the laser and astrophysical plasmas in the ultrarelativistic energy limit. In particular, we address basic mechanisms of the charged particle acceleration, the collisionless shock wave and magnetic reconnection and vortex dynamics properties relevant to the problem of ultrarelativistic particle acceleration.Comment: 58 pages, 19 figure