California Institute of Technology

William G Dunphy

Akiko Kumagai

Paul R Mueller

Thomas R Coleman

Zijian Guo

Akiko Kymagai

ATR kinase is a key regulator of checkpoint responses to incompletely replicated and damaged DNA. Without this checkpoint, cells will enter mitosis prematurely, likely resulting in cell death. The invention provides methods and reagents to either block or activate the activation of the ATR kinase checkpoint, through, for example, either blocking or activating the expression of an ATR activator TopBP1. The invention also provides screening methods to identify additional ToBP1 inhibitors or activators that may be used to modulate the activity of the ATR checkpoint.

Methods for modulating checkpoint activation through TopBP1

The present invention provides compositions of ATR nucleic acids and proteins, as well as methods of using said compositions in screening assays. The invention further provides antibodies and transgenic animals based on the ATR compositions.

Cloning and functional assays of Xenopus ATR

Claspin proteins and nucleotides encoding Claspin proteins are provided. Also provided is a method for identifying a compound that modulates cell cycle progression. A method is further provided for modulating cell cycle progression.

Claspin proteins and methods of use thereof

The present invention provides polypeptides (Cds1) that are involved in regulating the progression of the cell cycle. The polypeptides are activated by double-stranded DNA and phosphorylated in response to the presence of double-stranded DNA. Also provided are polynucleotides encoding Cds1 polypeptidese and methods for modulating cell cycle progression in a cell.

Checkpoint-activating oligonucleotides

The present invention provides a threonine/tyrosine kinase, Myt1, that phosphorylates the cyclin-dependent kinase, Cdc2, to provide regulation of the cell cycle at the G2/M interphase. Also included are polynucleotides encoding Myt1 polypeptide and antibodies that bind to Myt1. Methods of modulating Myt1 for preventing premature entry of the cell into mitosis or to accelerate entry into mitosis are also provided, as are methods for identifying agents that modulate Myt1.

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Altadena, CA, United States of America

William G Dunphy