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.
Orre
Lukas M
LM
Cancer Center Karolinska Institutet, Department of Oncology and Pathology, Division of Medical Radiation Biology, CCK R8:00 Karolinska Institute, SE-171 76 Stockholm, Sweden.
Fält
Susann
S
Szeles
Anna
A
Lewensohn
Rolf
R
Wennborg
Anders
A
Flygare
Jenny
J
D000199:Actins / Q000378:metabolism; D020137:Base Pair Mismatch; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism* / Q000502:physiology; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic
D000199:Actins; D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase