Human CtIP promotes DNA end resection

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.     

Zum Fabismus als Erbleiden

Summary Analysis of 100 families with at last one affected offspring seems conclusive for the assumption that favism is an inherited condition and that the responsible gene is a recessive one. The penetrance of the gene seems to be high and the expression stronger in males.     

Metachromasia in cultured fibroblasts of subjects with glycogenosis type II

Riassunto Frammenti di cute di due soggetti affetti da glicogenosi tipo II e dei loro genitori e fratelli sono stati coltivati in vitro. Sia nelle culture dei pazienti che dei loro familiari si è osservata la presenza di materiale metacromatico dopo colorazione con blu di toluidina 0. Nei leucociti di tutti i familiari esaminati l'attività della -1,4-glucosidasi è risultata ridotta.     

Biogenesis of rifamycins. The conversion of rifamycin B into rifamycin Y

Riassunto È stata studiata la biogenesi della rifamicina Y, prodotta accanto alla rifamicina B da culture diS. mediterranei. I dati riportati dimostrano che la rifamicina Y deriva dalla rifamicina Be che la sua produzione dipende dalla concentrazione di fosfati nel terreno di cultura.

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Presented in part at the Vth International Congress of Chemotherapy, Wien, 26 June 1967.     

Microburetta di precisione senza rubinetti

Zusammenfassung Es wird eine neue Präzisionsmikrobürette beschrieben, die es gestattet, Lösungen, die gegenüber Quecksilber indifferent sind, bis auf ungefähr 1/10 mm³ zu messen. Im Gegensatz zu den bisher üblichen Mikrobüretten hat sie keine Hahnen und verfettet daher nicht.     

Phosphorylation and activation of the atypical kinase p53-related protein kinase (PRPK) by Akt/PKB

p53-related protein kinase (PRPK), the human homologue of yeast Bud32, belonging to a small subfamily of atypical protein kinases, is inactive unless it is previously incubated with cell lysates. Here we show that such an activation of PRPK is mediated by another kinase, Akt/PKB, which phosphorylates PRPK at Ser250. We show that recombinant PRPK is phosphorylated in vitro by Akt and its phospho-form is recognized by a Ser250-phospho-specific antibody; that cell co-transfection with Akt along with wild-type PRPK, but not with its Ser250Ala mutant, results in increased PRPK phosphorylation; and that the phosphorylation of p53 at Ser15, the only known substrate of PRPK, is markedly increased by co-transfection of Akt with wild-type PRPK, but not PRPK dead mutant, and is abrogated by cell treatment with the Akt pathway inhibitor LY294002. Our data disclose an unanticipated mechanism by which PRPK can be activated and provide a functional link between this enigmatic kinase and the Akt signaling pathway.