Biomedical subjects

Lukas M Orre

Publications and source records attributed to Lukas M Orre.

2 recordsLinked to original sources

PubMed2006

p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line.

We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation.

Cell Line, Tumor↗

PubMed2006

Rad51-related changes in global gene expression.

High expression of Rad51, the catalytic component in homologous recombination, has been reported to contribute to genomic instability. To elucidate biological processes related to Rad51, we performed global gene expression analysis on human fibrosarcoma cells induced to express variable Rad51 levels. The results indicate that Rad51 overexpression mediates late rather than early transcriptional responses. Using Gene Ontology analysis, we extracted functional annotations for Rad51-related changes in gene expression that were independent of general cell culture effects. High Rad51 levels conferred increased expression of genes involved in actin remodelling. These changes were accompanied by alterations in cell morphology. Moreover, core components of the mismatch repair (MMR) machinery were down-regulated in response to increased Rad51 expression. Given the role of MMR in the correction of DNA mismatches during replication and recombination, a concurrent increase in Rad51 levels and decrease in the expression of MMR genes could conceivably act synergistically towards genomic instability.

Actins↗