Biomedical subjects

Lena Ström

Publications and source records attributed to Lena Ström.

6 recordsLinked to original sources

PubMed2006

Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways.

The SMC protein complexes safeguard genomic integrity through their functions in chromosome segregation and repair. The chromosomal localization of the budding yeast Smc5/6 complex determined here reveals that the complex works specifically on the duplicated genome in differently regulated pathways. The first controls the association to centromeres and chromosome arms in unchallenged cells, the second regulates the association to DNA breaks, and the third directs the complex to the chromosome arm that harbors the ribosomal DNA arrays. The chromosomal interaction pattern predicts a function that becomes more important with increasing chromosome length and that the complex's role in unchallenged cells is independent of DNA damage. Additionally, localization of Smc6 to collapsed replication forks indicates an involvement in their rescue. Altogether this shows that the complex maintains genomic integrity in multiple ways, and evidence is presented that the Smc5/6 complex is needed during replication to prevent the accumulation of branched chromosome structures.

Cell Cycle Proteins↗

PubMed2005

DNA damage-induced cohesion.

The protein complex Cohesin, forming protein-links that hold sister chromatids together, is at the heart of chromatid cohesion. Cohesion is important both for correct chromosome segregation and double-strand break (DSB) repair, making Cohesin central for the maintenance of genome stability. Until now, establishment of Cohesin links between chromatids has been shown to occur during DNA replication only. Recently it was however observed that in cells arrested in G2/M, DSB induction not only elicits chromosomal recruitment of Cohesin, but also formation of chromatid cohesion. The establishment of cohesion outside the period of replication opens a new field of investigation. Here we present results further supporting the formation of sister chromatid cohesion in response to DNA damage, and propose a model of how damage-induced cohesion could contribute to the linkage of chromatids during normal cell cycle progression.

Cell Cycle↗

PubMed2004

Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair.

Chromosome stability depends on accurate chromosome segregation and efficient DNA double-strand break (DSB) repair. Sister chromatid cohesion, established during S phase by the protein complex cohesin, is central to both processes. In the absence of cohesion, chromosomes missegregate and G2-phase DSB repair fails. Here, we demonstrate that G2-phase repair also requires the presence of cohesin at the damage site. Cohesin components are shown to be recruited to extended chromosome regions surrounding DNA breaks induced during G2. We find that in the absence of functional cohesin-loading proteins (Scc2/Scc4), the accumulation of cohesin at DSBs is abolished and repair is defective, even though sister chromatids are connected by S phase generated cohesion. Evidence is also provided that DSB induction elicits establishment of sister chromatid cohesion in G2, implicating that damage-recruited cohesin facilitates DNA repair by tethering chromatids.

Cell Cycle Proteins↗

PubMed2003

Binding of Ikaros to germline Ig heavy chain gamma1 and epsilon promoters.

Immunoglobulin (Ig) class switching occurs in activated B cells and results in production of antigen-specific IgA, IgE or IgG. It involves a DNA recombination event and is partly regulated by germline (GL) immunoglobulin heavy chain promoters. Ikaros is an abundant nuclear protein expressed in hematopoietic cells. Many different functions have been ascribed to Ikaros, such as transcriptional activation or repression, cell cycle control and tumor suppression. A typical feature of Ikaros is its expression in large clusters in the nucleus of activated lymphocytes. We give evidence that Ikaros can bind to several sites in the germline gamma1 and epsilon immunoglobulin heavy chain promoters, in a cooperative manner. Using a promoter reporter assay, we found evidence that Ikaros can suppress germline gamma1 and epsilon promoter activity in a B cell line. When a mutated non-DNA-binding form of Ikaros was introduced into primary activated B cells by retrovirus transduction, the endogenous Ikaros clusters were disrupted. In spite of this, there was no effect on transcription or Ig class switching. The data are discussed in relation to the different hypotheses for the function of Ikaros.

Animals↗

PubMed2002

Exposure to anti-cancer drugs during preparation and administration. Investigations of an open and a closed system.

Systems for the preparation and administration of drugs are designed to ensure that the drug is not contaminated. They do not necessarily consider the work environment for the medical staff and new techniques are therefore desirable. The aim of this work is to compare a new closed system for the preparation and administration of drugs with the traditional technique with regard to airborne emission and surface spillage of drugs. Platinum, determined using adsorptive voltammetry, was used as the tracer for airborne emission. Air samples were collected during the preparation and administration, and the collected platinum on the filters was determined by adsorptive voltammetry. For determination of spills and leakage onto surfaces the radioisotope 99m-technetium was used as a tracer. The radiation from the isotope was determined on protective gloves and bench covers after preparation and administration. The mean airborne emission was 6 ng m(-3) with the closed system and 15 ng m(-3) with the traditional pump technique. The average surface spillage using the closed technique was 0.005 microL. This is significantly smaller than with the traditional technique, which resulted in an average spillage of 64 microL. Our results also show that the dominant part of the leakage is surface spillage. Inexperienced nurses could also adequately handle the closed system.

Accidents, Occupational↗

PubMed2002

Cisplatin contamination observed on the outside of drug vials.

Exposure to cytotoxic drugs is of great concern today. Special regulations for handling these drugs during preparation and administration have been implemented in most countries. Concern has also been raised as to whether exposure to these drugs can occur due to contaminated drug vials. In this investigation, wipe samples were taken from drug vials used for platinum-containing drugs, e.g. cisplatin and related drugs. The vials were randomly picked from unbroken packages from different manufacturers. The results showed that drug vials may already be contaminated on the outside when delivered from the manufacturer.

Cisplatin↗