Both Chromosome Decondensation and Condensation Are Dependent on DNA Replication in C.elegans Embryos

SummaryDuring cell division, chromatin alternates between a condensed state to facilitate chromosome segregation and a decondensed form when DNA replicates. In most tissues, S phase and mitosis are separated by defined G1 and G2 gap phases, but early embryogenesis involves rapid oscillations between replication and mitosis. Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA. In addition, we found that, during late telophase, replication initiates on condensed chromosomes and promotes the rapid decondensation of the chromatin. Upon replication initiation, the CDC-45-MCM-GINS (CMG) DNA helicase drives the release of condensin I complexes from chromatin and the activation or displacement of inactive MCM-2–7 complexes, which together with the nucleoporin MEL-28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation. Our results show how, in an early embryo, the chromosome-condensation cycle is functionally linked with DNA replication

Brief Announcement: Hamming Distance Completeness and Sparse Matrix Multiplication

We show that a broad class of (+, diamond) vector products (for binary integer functions diamond) are equivalent under one-to-polylog reductions to the computation of the Hamming distance. Examples include: the dominance product, the threshold product and l_{2p+1} distances for constant p. Our results imply equivalence (up to poly log n factors) between complexity of computation of All Pairs: Hamming Distances, l_{2p+1} Distances, Dominance Products and Threshold Products. As a consequence, Yuster\u27s (SODA\u2709) algorithm improves not only Matousek\u27s (IPL\u2791), but also the results of Indyk, Lewenstein, Lipsky and Porat (ICALP\u2704) and Min, Kao and Zhu (COCOON\u2709). Furthermore, our reductions apply to the pattern matching setting, showing equivalence (up to poly log n factors) between pattern matching under Hamming Distance, l_{2p+1} Distance, Dominance Product and Threshold Product, with current best upperbounds due to results of Abrahamson (SICOMP\u2787), Amir and Farach (Ann. Math. Artif. Intell.\u2791), Atallah and Duket (IPL\u2711), Clifford, Clifford and Iliopoulous (CPM\u2705) and Amir, Lipsky, Porat and Umanski (CPM\u2705). The resulting algorithms for l_{2p+1} Pattern Matching and All Pairs l_{2p+1}, for 2p+1 = 3,5,7,... are new. Additionally, we show that the complexity of AllPairsHammingDistances (and thus of other aforementioned AllPairs- problems) is within poly log n from the time it takes to multiply matrices n x (n * d) and (n * d) x n, each with (n * d) non-zero entries. This means that the current upperbounds by Yuster (SODA\u2709) cannot be improved without improving the sparse matrix multiplication algorithm by Yuster and Zwick (ACM TALG\u2705) and vice versa

Un R\'esultat de Compl\'etude pour les Types ∀+\forall^+ du Syst\`eme F

We presente in this note a completeness result for the types with positive quantifiers of the J.-Y. Girard type system F. This result generalizes a theorem of R. Labib-Sami

Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin.

The eukaryotic replisome disassembles parental chromatin at DNA replication forks, but then plays a poorly understood role in the re-deposition of the displaced histone complexes onto nascent DNA. Here, we show that yeast DNA polymerase α contains a histone-binding motif that is conserved in human Pol α and is specific for histones H2A and H2B. Mutation of this motif in budding yeast cells does not affect DNA synthesis, but instead abrogates gene silencing at telomeres and mating-type loci. Similar phenotypes are produced not only by mutations that displace Pol α from the replisome, but also by mutation of the previously identified histone-binding motif in the CMG helicase subunit Mcm2, the human orthologue of which was shown to bind to histones H3 and H4. We show that chromatin-derived histone complexes can be bound simultaneously by Mcm2, Pol α and the histone chaperone FACT that is also a replisome component. These findings indicate that replisome assembly unites multiple histone-binding activities, which jointly process parental histones to help preserve silent chromatin during the process of chromosome duplication

DONSON is required for CMG helicase assembly in the mammalian cell cycle

DONSON is one of 13 genes mutated in a form of primordial microcephalic dwarfism known as Meier-Gorlin Syndrome. The other 12 encode components of the CDC45-MCM-GINS helicase, around which the eukaryotic replisome forms, or are factors required for helicase assembly during DNA replication initiation. A role for DONSON in CDC45-MCM-GINS assembly was unanticipated, since DNA replication initiation can be reconstituted in vitro with purified proteins from budding yeast, which lacks DONSON. Using mouse embryonic stem cells as a model for the mammalian helicase, we show that DONSON binds directly but transiently to CDC45-MCM-GINS during S-phase and is essential for chromosome duplication. Rapid depletion of DONSON leads to the disappearance of the CDC45-MCM-GINS helicase from S-phase cells and our data indicate that DONSON is dispensable for loading of the MCM2-7 helicase core onto chromatin during G1-phase, but instead is essential for CDC45-MCM-GINS assembly during S-phase. These data identify DONSON as a missing link in our understanding of mammalian chromosome duplication and provide a molecular explanation for why mutations in human DONSON are associated with Meier-Gorlin syndrome