Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis
| Autor: | W Goedecke, Hildo H. Offenberg, Christa Heyting, Maureen Eijpe, M. van Aalderen |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
DNA repair Fluorescent Antibody Technique CHO Cells Biology Models Biological Bivalent (genetics) Chromosome segregation Mice Meiosis Cricetinae Testis Genetics Homologous chromosome Escherichia coli Animals Humans Mitosis Ku Autoantigen Recombination Genetic Ku70 MRE11 Homologue Protein fungi DNA Helicases Nuclear Proteins Antigens Nuclear Molecular biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) DNA Repair Enzymes Gene Expression Regulation Homologous recombination Plasmids Protein Binding |
| Zdroj: | Nature genetics. 23(2) |
| ISSN: | 1061-4036 |
| Popis: | Double-strand DNA breaks (DSBs) pose a major threat to living cells, and several mechanisms for repairing these lesions have evolved. Eukaryotes can process DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ). NHEJ connects DNA ends irrespective of their sequence, and it predominates in mitotic cells, particularly during G1 (ref. 3). HR requires interaction of the broken DNA molecule with an intact homologous copy, and allows restoration of the original DNA sequence. HR is active during G2 of the mitotic cycle and predominates during meiosis, when the cell creates DSBs (ref. 4), which must be repaired by HR to ensure proper chromosome segregation. How the cell controls the choice between the two repair pathways is not understood. We demonstrate here a physical interaction between mammalian Ku70, which is essential for NHEJ (ref. 5), and Mre11, which functions both in NHEJ and meiotic HR (Refs 2,6). Moreover, we show that irradiated cells deficient for Ku70 are incapable of targeting Mre11 to subnuclear foci that may represent DNA-repair complexes. Nevertheless, Ku70 and Mre11 were differentially expressed during meiosis. In the mouse testis, Mre11 and Ku70 co-localized in nuclei of somatic cells and in the XY bivalent. In early meiotic prophase, however, when meiotic recombination is most probably initiated, Mre11 was abundant, whereas Ku70 was not detectable. We propose that Ku70 acts as a switch between the two DSB repair pathways. When present, Ku70 destines DSBs for NHEJ by binding to DNA ends and attracting other factors for NHEJ, including Mre11; when absent, it allows participation of DNA ends and Mre11 in the meiotic HR pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|