- Centre for Cancer Research - Research Publications
Centre for Cancer Research - Research Publications
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ItemInter-subunit interactions that coordinate Rad51s activitiesGrigorescu, AA ; Vissers, JHA ; Ristic, D ; Pigli, YZ ; Lynch, TW ; Wyman, C ; Rice, PA (OXFORD UNIV PRESS, 2009-02)Rad51 is the central catalyst of homologous recombination in eukaryotes and is thus critical for maintaining genomic integrity. Recent crystal structures of filaments formed by Rad51 and the closely related archeal RadA and eubacterial RecA proteins place the ATPase site at the protomeric interface. To test the relevance of this feature, we mutated conserved residues at this interface and examined their effects on key activities of Rad51: ssDNA-stimulated ATP hydrolysis, DNA binding, polymerization on DNA substrates and catalysis of strand-exchange reactions. Our results show that the interface seen in the crystal structures is very important for nucleoprotein filament formation. H352 and R357 of yeast Rad51 are essential for assembling the catalytically competent form of the enzyme on DNA substrates and coordinating its activities. However, contrary to some previous suggestions, neither of these residues is critical for ATP hydrolysis.
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ItemThe many faces of ubiquitinated histone H2A: insights from the DUBsVissers, JHA ; Nicassio, F ; van Lohuizen, M ; Di Fiore, PP ; Citterio, E (BMC, 2008)Monoubiquitination of H2A is a major histone modification in mammalian cells. Understanding how monoubiquitinated H2A (uH2A) regulates DNA-based processes in the context of chromatin is a challenging question. Work in the past years linked uH2A to transcriptional repression by the Polycomb group proteins of developmental regulators. Recently, a number of mammalian deubiquitinating enzymes (DUBs) that catalyze the removal of ubiquitin from H2A have been discovered. These studies provide convincing evidence that H2A deubiquitination is connected with gene activation. In addition, uH2A regulatory enzymes have crucial roles in the cellular response to DNA damage and in cell cycle progression. In this review we will discuss new insights into uH2A biology, with emphasis on the H2A DUBs.