Featured Review Cellscience Reviews Vol 5 No 1 ISSN 1742-8130

Chromosome damage repair: strategies and complications
in targeting the BRCA2-PALB2 axis for cancer therapy

The integrity of our genetic blueprint can be easily compromised because of the labile nature of DNA. Specifically, DNA can be damaged by a multitude of agents, including high-energy radiations and man-made chemicals that are prevalent in our environment and also reactive agents that arise through cellular metabolism. Moreover, complex lesions arise during DNA replication, when replicative DNA polymerases encounter a pre-existing lesion or an unusual structure in the DNA template. If not dealt with properly, the DNA damage can cause mutations and even chromosome rearrangements. These undesirable genetic changes can then lead to cancer formation. Fortunately, all living organisms possess efficient DNA repair systems to minimize this threat. Here, we discuss how one particularly harmful type of DNA damage – the DNA double-stranded break – is removed by a repair process called homologous recombination. We also survey recent advances in exploiting homologous recombination deficiency in cancer therapy and highlight the complications associated with this approach.

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