Double stranded breaks (DSBs) are a normal occurrence during DNA replication. The cellular response to DSBs is complex and highly orchestrated, and a cell’s inability to properly address DSBs can lead to genetic alterations such as loss of heterozygosity, mutations, deletions, genomic rearrangements, and chromosome loss. There are two major pathways for repairing DSBs: non-homologous end joining (NHEJ) and homologous recombination (HR). Both pathways are critical to the maintenance of genomic stability and involve a variety of proteins that play particular functional roles in the response to DNA damage. In HR, the functional groups include the DNA damage sensors, cell cycle checkpoint enforcers, and the catalyzers of HR repair itself. Additionally, the HR repair pathway requires proteins that function as adaptors and transducers, effector kinases, regulatory proteins, and structural components (1). There are several diseases associated with genetic defects in proteins involved in HR. These genetic diseases are characterized by a predisposition to cancer indicating the importance of intact HR pathways to circumvent cancer (2). Although deficiencies in HR lead to cancer development, these deficiencies also allow for the selective treatment of cancer cells. Anti-cancer drugs mainly kill cancer cells by inducing toxic DSBs and defects in HR can increase the sensitivity of cancer cells to these drugs (3). Therefore, a better understanding of the factors and pathways involved in HR will further advancements in the development of therapies for cancer.
1. Lisby, M. & Rothstein, R. (2009). Choreography of recombination proteins during the DNA damage response. DNA Repair (Amst), 8, 1068-1076.
2. Thompson, L. H. & Schild, D. (2002). Recombinational DNA repair and human disease. Mutat.Res., 509, 49-78.
3. Helleday, T. (2010). Homologous recombination in cancer development, treatment and development of drug resistance. Carcinogenesis, 31, 955-960.