Homologous recombination maintenance of genome integrity during DNA damage tolerance.
The DNA strand exchange protein Rad51 provides a safe mechanism for the repair of DNA breaks using the information of a homologous DNA template. Homologous recombination (HR) also plays a key role in the response to DNA damage that impairs the advance of the replication forks by providing mechanisms to circumvent the lesion and fill in the tracks of single-stranded DNA that are generated during the process of lesion bypass. These activities postpone repair of the blocking lesion to ensure that DNA replication is completed in a timely manner. Experimental evidence generated over the last few years indicates that HR participates in this DNA damage tolerance response together with additional error-free (template switch) and error-prone (translesion synthesis) mechanisms through intricate connections, which are presented here. The choice between repair and tolerance, and the mechanism of tolerance, is critical to avoid increased mutagenesis and/or genome rearrangements, which are both hallmarks of cancer.
Departamento de Biología Molecular; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) ; Consejo Superior de Investigaciones Científicas (CSIC) ; Seville, Spain.
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BRCA2; DNA damage tolerance; DNA repair homologous recombination; Rad18; Rad51; replication