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Content archived on 2024-05-29

Investigating the role of the Smc5/6 complex during DNA replication and repair of DNA.

Final Activity Report Summary - EIF-SMC5/6 COMPLEX (Investigating the role of the Smc5/6 complex during DNA replication and repair of DNA.)

DNA double-strand breaks (DSB) are one of the most common and threatening alterations of a cell's genetic material. Left unrepaired, DSBs can cause cell death and, if misrepaired, they can lead to genomic instability and the development of cancer in multicellular organisms. DNA double-strand breaks can occur during DNA replication or after DNA damage. The Smc5-Smc6 complex was initially discovered through a genetic screen looking for radiation-sensitive mutants in fission yeast (Structural maintenance of chromosomes = SMC). The Smc5-Smc6 complex is conserved from yeast to human and in yeast all subunits are essential. The complex is involved in DNA repair and is required for the stability of the repetitive ribosomal gene cluster in budding yeast.

In my project I could demonstrate that following a single DSB induced by the HO endonuclease system, Smc5-Smc6 subunits are recruited to the vicinity of the break de novo. Physical analysis of the repair of induced DSBs in smc5-smc6 mutants reveals that inactivation of the complex reduces sister chromatid recombination (SCR). I could also show that Smc5-Smc6 do not significantly contribute to the religation of a DSB by the 'non-homologous end joining' (NHEJ) repair pathway. These findings demonstrate that the Smc5-Smc6 complex is essential to maintain genome stability because it directs repair of replication-induced DSBs through error-free sister chromatid recombination pathways, thus suppressing inappropriate non-sister recombination events.