Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing

Checkpoints maintain order and fidelity in the cell cycle by blocking late-occurring events when earlier events are improperly executed. Here we describe evidence for the participation of Chk1 in an intra-S phase checkpoint in mammalian cells. We show that both Chk1 and Chk2 are phosphorylated and activated in a caffeine-sensitive signaling pathway during S phase, but only in response to replication blocks, not during normal S phase progression. Replication block–induced activation of Chk1 and Chk2 occurs normally in ataxia telangiectasia (AT) cells, which are deficient in the S phase response to ionizing radiation (IR). Resumption of synthesis after removal of replication blocks correlates with the inactivation of Chk1 but not Chk2. Using a selective small molecule inhibitor, cells lacking Chk1 function show a progressive change in the global pattern of replication origin firing in the absence of any DNA replication. Thus, Chk1 is apparently necessary for an intra-S phase checkpoint, ensuring that activation of late replication origins is blocked and arrested replication fork integrity is maintained when DNA synthesis is inhibited

Intranuclear changes in cancer cells

A report on the FASEB meeting 'Nuclear Structure and Cancer', Saxtons River, USA, 16-21 June 2007

Analysis of the individual risk of altitude decompression sickness under repeated exposures

In a case-control study, researchers examined the risk of decompression sickness (DCS) in individual subjects with higher number of exposures. Of the 126 subjects, 42 showed one or more episodes of DCS. Examination of the exposure-DCS relationship by odds ratio showed a linear relationship. Stratification analysis showed that sex, tissue ratio, and the presence of Doppler microbubbles were cofounders of this risk. A higher number of exposures increased the risk of DCS in this analysis

Lovastatin arrests CHO cells between the origin decision point and the restriction point

AbstractAsynchronously growing Chinese hamster ovary (CHO) cells treated with the pro-drug, β-lactone ring form of lovastatin were arrested in G1-phase. Subsequent removal of lovastatin resulted in the synchronous entry of cells into S-phase regardless of the presence of mevalonic acid. Lovastatin-arrested cells contained hypophosphorylated retinoblastoma protein (Rb) and required serum mitogens to enter S-phase after lovastatin removal, indicating that cell-cycle arrest is prior to the restriction point (R-point). However, in contrast to quiescent cells, intact nuclei prepared from lovastatin-arrested cells were competent for DNA replication when introduced into Xenopus egg extracts. Initiation of replication by Xenopus egg cytosol took place specifically within the dihydrofolate reductase (DHFR) origin locus, demonstrating that cells were arrested after the origin decision point (ODP). We conclude that the β-lactone ring form of lovastatin is an effective reagent with which to synchronize CHO cells between the ODP and R-point, without resulting in the withdrawal of cells from the cell-cycle into a quiescent state

Adaptive Compression of Graph Structured Text

In this paper we introduce an adaptive technique for compressing small quantities of text which are organized as a rooted directed graph. We impose a constraint on the technique such that data encountered during a traversal of any valid path through the graph must be recoverable without requiring the expansion of data that is not on the path in question. The technique we present determines the set of nodes y which are guaranteed to be encountered before reaching node x while traversing any valid path in the graph, and uses them as a basis for conditioning an LZW dictionary for the compression/expansion of the data in x. Initial results show that our improved LZW technique reduces the compressed text size by approximately 20 % more than regular LZW, and requires only minor modifications to the standard LZW decompression routine.

Proliferation-dependent and cell cycle–regulated transcription of mouse pericentric heterochromatin

Pericentric heterochromatin transcription has been implicated in Schizosaccharomyces pombe heterochromatin assembly and maintenance. However, in mammalian systems, evidence for such transcription is inconsistent. We identify two populations of RNA polymerase II–dependent mouse γ satellite repeat sequence–derived transcripts from pericentric heterochromatin that accumulate at different times during the cell cycle. A small RNA species was synthesized exclusively during mitosis and rapidly eliminated during mitotic exit. A more abundant population of large, heterogeneous transcripts was induced late in G1 phase and their synthesis decreased during mid S phase, which is coincident with pericentric heterochromatin replication. In cells that lack the Suv39h1,2 methyltransferases responsible for H3K9 trimethylation, transcription occurs from more sites but is still cell cycle regulated. Transcription is not detected in quiescent cells and induction during G1 phase is sensitive to serum deprivation or the cyclin-dependent kinase inhibitor roscovatine. We demonstrate that mammalian pericentric heterochromatin transcription is linked to cellular proliferation. Our data also provide an explanation for inconsistencies in the detection of such transcripts in different systems

A New Design for Open and Scalable Collaboration of Independent Databases in Digitally Connected Enterprises

“Digitally connected enterprises” refers to e-business, global supply chains, and other new business designs of the Knowledge Economy; all of which require open and scalable information supply chains across independent enterprises. Connecting proprietarily designed and controlled enterprise databases in these information supply chains is a critical success factor for them. Previous connection designs tend to rely on “hard-coded” regimes, which do not respond well to disruptions (including changes and failures), and do not afford these enterprises sufficient flexibility to join simultaneously in multiple supply chain regimes and share information for the benefit of all. The paper develops a new design: It combines matchmaking with global database query, and thereby supports the interoperation of independent databases to form on-demand information supply chains. The design provides flexible (re-)configuration to decrease the impact of disruption, and proactive control to increase collaboration and information sharing. More broadly, the papers results contribute to a new Information System design method for massively extended enterprises, and facilitate new business designs using digital connections at the level of databases