Double-Strand Break Repair in E. coli

DNA heteroduplex extension % CDcri 3 (Double HoUifeyJuhdloitt 5 1 3 Branch migration proteins (RuvAB and RecG) 

2 Double-Strand Break Repair in Eukaryotic Cells 

Eukaryotic cells possess two pathways for the repair of DSBs. One pathway is homologous recombination and appears to be very similar to the one described above in E. coli. However, much less is known about the details of this pathway in mammalian cells. In yeast, homologous recombination is the major pathway for the repair of DSBs. In mammalian cells it is restricted to the late S and G2 phases of the cell cycle. The second pathway is called nonhomologous end joining (NHEJ), and it is thought to be the major pathway for the repair of DSBs in mammalian cells. The two pathways differ in the proteins that participate in them, and they also significantly differ in the outcomes they produce. Homologous recombination produces few errors, whereas NHEJ is error-prone. 

The homologous recombination repair pathway is highly complex, in part perhaps as a consequence of the diverse collection of structures on which it acts. Many proteins have been implicated in this pathway, but their real specific roles in the 

Rothmund-Thomson (Recql 4) proteins. The genes that encode these proteins are altered in human syndromes of the same name. Patients with these diseases are predisposed to different forms of cancer. Cell lines derived from patients with these diseases exhibit chromosome instability and accumulate abnormal replication intermediates. When these helicase proteins are studied in vitro, they can unwind Holliday junction-like structures. A characteristic of many proteins involved in homologous recombination is that they can be visualized as forming subnuclear structures in cells in response to DNA damage. This can be directly visualized using immunofluorescence and the structures that are formed are called foci (see Section 23.8.2). 

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