Biomedical subjects

S Handeli

Publications and source records attributed to S Handeli.

3 recordsLinked to original sources

PubMed1992

The ts41 mutation in Chinese hamster cells leads to successive S phases in the absence of intervening G2, M, and G1.

The ts41 mutation of Chinese hamster cells was first isolated and characterized by Hirschberg and Marcus (1982) who showed that at nonpermissive temperature, cells accumulate up to 16C equivalents of DNA. Here we show that the mutation is recessive and at nonpermissive temperature, cells replicate their genome normally, but instead of going on into G2, M, and G1, they pass directly into a second S phase. Entry into a second S phase does not require serum nor is it inhibited by G2 checkpoints or mitotic inhibitors. Temperature-shift experiments suggest that the ts41 gene product participates in two functions in the cell cycle: entry into mitosis and inhibition of entry into S phase. The ts41 mutation seems to define a class of cell cycle mutant that couples the sequential events of DNA replication and mitosis.

Animals↗

PubMed1989

Mapping replication units in animal cells.

A general approach for assaying the in vivo direction of replication for any DNA segment has been developed. This technique allows the scanning of genomic regions to detect bidirectional tail-to-tail replication, indicating the presence of a functional origin. By this criterion we identified the approximate positions of two origin sites downstream of the Chinese hamster DHFR gene. Further mapping revealed areas of head-to-head replication, signifying locations of replication termination and thus defining the landmarks of a complete animal cell replicon. Genetic proof for the existence of the DHFR origin was obtained by showing that this region serves as a bidirectional DNA synthesis initiation point following its integration into other sites in the genome by transfection. To show the general applicability of this methodology, we studied the APRT domain. Replication mapping together with the use of deletion mutants allowed the identification of an origin at a far-upstream locus.

Adenine Phosphoribosyltransferase↗

PubMed1986

Effects of red blood cell potassium and hypertonicity on the growth of Plasmodium falciparum in culture.

Malarial parasites reproduce asexually inside the erythrocytes of their vertebrate host. Relatively little is known about the interaction between host cell and parasite metabolism. In the present study the effect of host cell cation composition and osmotic shrinkage on in vitro growth and propagation of Plasmodium falciparum in human erythrocytes was investigated. It is shown that throughout the parasite cell cycle, infected cells lose potassium and gain sodium. Compartment analysis of infected cells revealed that host cell cytosol is poor in potassium and rich in sodium while in the parasite this relationship is reversed, indicating that the parasite is able to regulate its ionic composition independently. Parasites proceeded normally through their cell cycle in the presence of the sodium-pump inhibitor ouabain, although host cells lost up to 75-80% of their normal potassium content. Potassium-depleted erythrocytes harboring trophozoites and schizonts also display normal rates of protein synthesis as measured by isoleucine incorporation. Parasite growth was inhibited when infected cells were osmotically shrunken in hypertonic media, but this was not due to parasite dehydration. It is suggested that increased viscosity of host cell cytosol and/or hemoglobin gelation, are responsible for the effect, probably through interference with parasite feeding. The relevance of these results to understanding of the cellular mechanism involved in the inhibiton of parasite growth in deoxygenated sickle-trait erythrocytes is discussed.

Erythrocytes↗