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Doubleridge is a transgene-induced mutation characterized by polydactyly and syndactyly of the forelimbs. The transgene insertion maps to the proximal region of chromosome 19. During embryonic development of the mutant forelimb, delayed elevation and compaction of the apical ectodermal ridge (AER) produces a ridge that is abnormally broad and flat. Fgf8 expression persists in the ventral forelimb ectoderm of the mutant until E10.5. Strong expression of Fgf8 and other markers at the borders of the AER at E11.5 gives the appearance of a double ridge. At E11.5, apoptotic cells are distributed across the broadened ridge, but at E13.5, there is reduced apoptosis in the interdigital regions. The Shh expression domain is widely spaced at the posterior margin of the AER. The doubleridge AER is morphologically similar to that of En1 null mice, but the expression of En1 and Wnt7a is properly restricted in doubleridge, and the dorsal and ventral structures are correctly determined, doubleridge thus exhibits an unusual limb phenotype combining abnormal compaction of the AER with normal dorsal/ventral patterning. Keywords: Limb development; AER; Dorsal-ventral patterning; Fgf8; En1; Polydactyly; Syndactyly; Mouse

The authors review the publications on RNA-mediated interference. The topics of interest include chromosomal function mediation by RNA-mediated interference protein components and by short RNAs.

The authors review the publications on the nuclear envelope. The topics of interest include the ability of the spindle microtubule to access the chromosomes by opening the nucleus at the beginning of mitosis.

Research has been conducted on the sister chromatid separation in anaphase mediated by separase, an endopeptidase cleaving chromosomal cohesin SCC1. Results indicate that separase activity is inhibited by independent processes acting on separase itself, one is dependent on securin and the other is dependent on the inhibitory separase phosphorylation.

Research has been conducted on the mitotic checkpoint inhibiting the anaphase entry until the chromosomes have attached to spindle microtubules. The use of the Xenopus egg extracts in demonstrating that the yeast Mps1 vertebrate homolog is a kinetochore-associated kinase important for the establishing and maintaining the checkpoint is described.

Research has been conducted on the meiotic recombination intermediate occurring during the double-strand break transition to the double-Holliday junction. The identification of this intermediate has been carried out and the analysis of the single-end invasion structural asymmetry indicate that the two ends of the double-strand break interact with the homologue in the temporal succession via biochemically distinct process.

Research has been conducted on the regulator of chromosome condensation (RCC1), a guanine nucleotide exchange factor for the nuclear binding protein Ran. The crystal structure of the Ran.RCC1 complex has been examined in the absence of the nucleotide and the results indicate that the nucleoside binding site's phosphate binding region is perturbed marginally due to the presence of the polyvalent anion in the P loop.

The author presents a review of the publications on the chromosomes which play important role in mitosis. The points of interest include the biochemistry of Run, abundant and conserved GTPase, and its role in the nuclear transport and the relationship between Run and mitotic spindle assembly.

Cleavage of Rec8 by separin at one of two sites has been found to be necessary for the resolution of chiasmata and the disjunction of homologous chromosomes in meiosis. Noncleavable mutations were generated in Rec8's potential separin cleavage sites. Both sites were seen to be substrates for separin in vitro and in vivo.

Boundaries of imprinting are discussed in this review article, which deals with whether a switch that occurs in fission yeast and is determined by replication and by a replication pause site and other epigenetic phenomena in which chromosomal domains are heritably repressed might have things in common with the mechanisms used to set up or propagate imprinting in mammals. Topics include methylation-sensitive boundary element and mutually exclusive Igf2 and H19 expression, propagating epigenetic states in absence of initial stimulus, and replicating the chromatin landscape. Questions still exist relative to the silent imprinted alleles on mammal chromosomes.

Results demonstrate that in Saccharaomyces cerevisiae and Caenorhabditis elegans, the phosphorylation of histones plays a key role in the proper segregation of chromosomes in mitotic cell division. Data further indicate that aurora kinase and its genetically related phosphatase are involved in the phosphorylation process.

Results of two studies provide evidences that contend the classical view on telomere structure that claims that the binding of telomere proteins to telomeric DNA results to linear DNA molecules. It was, instead, found that telomeres in mammalian cells end as large terminal loops called T loops. The two studies observed that long stretches of the double-stranded telomere DNA are loped around while the single-stranded terminus is tucked back inside the double-stranded DNA molecule.

A copy of the E. coli lactose operon (lacO) cassette was inserted near the replication origin of Bacillus subtilis chromosome to determine the mechanisms of Bacillus subtilis chromosome segregation. The chromosomes of Bacillus subtilis are oriented with their origins near opposite poles during the initial phase of sporulation. The origin-distal region of the forespore chromosome was then translocated to the small sporangial compartment after polar septation. Finally, the replication origin separated near either end of the sporangium after the engulfment of the forespore by the mother cell.

Research points out that RecBCD helicase/nuclease is involved in the initiation of homologous recombination at double-stranded DNA breaks and that its interaction with chi affects translocation by RecBCD. Data indicate that RecBCD pauses precisely at chi during its translocation along DNA molecules. Furthermore, interaction with chi uncouples the RecD motor from RecBCD enzyme resulting in its slower translocase activity.

Research findings illustrate that global chromosome positions are heritable as shown by a following single chromosome positioning during mitosis, which is reflected in similarities between the progeny and the parent mammalian cells.