John Newport
e-mail: jnewport@ucsd.edu |
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My laboratory is interested in how multi-protein regulatory pathways participate in the function of essential cellular processes. In particular, we are interested in how proteins regulate: (1) the cell cycle, (2) the formation and function of nuclei, (3) the timing of early developmental events, and (4) programs which regulate cell death or apoptosis.
Our investigations on cell cycle regulation have concentrated on two processes: how regulation of cdc2 kinase activity participates in the initiation of mitosis, and how cdk2 kinase regulates the initiation of DNA replication. Together these regulatory networks ensure that the cell cycle progresses in an ordered manner from one function to the next.
Studies on nuclear structure have concentrated both on how the nuclear envelope reforms around chromosomes at the end of mitosis and how the organization of DNA into discrete sub-nuclear domains controls replication origin selection and initiation of DNA replication during S-phase of the cell cycle. These studies are designed to provide information about how the higher order structural features of the nucleus contribute to nuclear specific functions.
Our studies on developmental timers have focused on how mRNA and protein degradation programs are activated during early development. The timed activation of these degradative systems is essential for eliminating maternal programs and allowing new programs to take effect.
Lastly, we have recently begun investigating how the regulatory networks
which activate ICE-like proteases leading to cell death or apoptosis
are controlled. In particular, these studies have focused on the molecular
links which may exist between the cell cycle and the cell death regulatory
pathways. All of these investigations are undertaken using Xenopus
eggs and cell-free extracts made from these eggs as a working
system and using molecular and biochemical techniques to identify,
purify, and modify the activities of interest.
Yamaguchi R, Newport J. (2003). A
Role for Ran-GTP and Crm1 in Blocking Re-Replication. Cell. 113(1):115-25.
You Z, Harvey K, Kong L, Newport J. (2002).
Xic1 degradation in Xenopus egg extracts is coupled to initiation
of DNA replication. Genes Dev. 16(10):1182-94.
You Z, Kong L, Newport J. (2002). The
role of single-stranded DNA and polymerase alpha in establishing
the ATR, Hus1 DNA replication checkpoint. J Biol Chem. 277(30):27088-93.
Michael WM, Ott R, Fanning E, Newport
J. (2000). Activation of the DNA replication checkpoint through
RNA synthesis by primase. Science. 289(5487):2133-7.
Walter J, Newport J. (2000). Initiation
of eukaryotic DNA replication: origin unwinding and sequential
chromatin association of Cdc45, RPA, and DNA polymerase alpha.
Mol Cell. 5(4):617-27.
Michael WM, Newport J. (1998). Coupling
of mitosis to the completion of S phase through Cdc34-mediated
degradation of Wee1. Science. 282(5395):1886-9.
John Newport received his Ph.D. from the University of Oregon. He was a postdoctoral fellow with the Department of Biochemistry and Biophysics at the University of California, San Francisco.
