Homologous recombination deficiency: how genomic signatures are generated.

Cancer genomes harbor mutational and structural rearrangements that are jointly shaped by DNA damage and repair mechanisms. Accumulating evidence suggests that genetic alterations in DNA repair-defective tumors reflect the scars caused by the use of backup DNA repair mechanisms needed to maintain cellular viability. Detailed analysis of the patterns of mutations and structural rearrangements present in BRCA1/2-deficient tumors has allowed for the delineation of genomic signatures that reflect alternative repair with inactive homologous recombination (HR). Here we aim to summarize recent advances in the analysis of genomic signatures associated with HR-deficiency and examine recent studies that have shed light on the backup repair mechanisms responsible for genomic scarring in HR-deficient tumors.