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The DNA damage response: making it safe to play with knives.
This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals. Expand
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
The data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling. Expand
ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage
A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR is performed and more than 900 regulated phosphorylation sites encompassing over 700 proteins are identified. Expand
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. To identify potential Cdk2 regulators, we have… Expand
The DNA damage response: putting checkpoints in perspective
The inability to repair DNA damage properly in mammals leads to various disorders and enhanced rates of tumour development, and this work has shown that direct activation of DNA repair networks is needed to correct this problem. Expand
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.
It is shown that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU). Expand
The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
An improved version of the yeast two-hybrid system is developed and used to isolate human cDNAs encoding proteins able to bind p110RB to demonstrate that PP-1 alpha isoforms preferentially bind the hypophosphorylated form of p110 RB. Expand
SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box
Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle. Expand
Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
The structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF complex suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold. Expand
The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus
It is discovered that the interferon-inducible transmembrane proteins IFITM1, 2, and 3 restrict an early step in influenza A viral replication. Expand