Since DNA double-strand breaks (DSBs) contribute to the genomic instability that drives cancer development, DSB repair pathways serve as important mechanisms for tumor suppression. Thus, genetic lesions, such as BRCA1 and BRCA2 mutations, that disrupt DSB repair are often associated with cancer susceptibility.

A deletion changes the DNA sequence by removing at least one nucleotide in a gene. Small deletions remove one or a few nucleotides within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the affected protein or proteins.

Proofreading by DNA polymerase corrects errors during replication. Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair ((Figure)).

Fortunately, cells have evolved highly sophisticated means of fixing most, but not all, of those mistakes. Some of the mistakes are corrected immediately during replication through a process known as proofreading, and some are corrected after replication in a process called mismatch repair.

Most damage to DNA is repaired by removal of the damaged bases followed by resynthesis of the excised region. Some lesions in DNA, however, can be repaired by direct reversal of the damage, which may be a more efficient way of dealing with specific types of DNA damage that occur frequently.

Double-strand DNA breaks—the most dangerous form of DNA damage, which can lead to cancer—don’t happen randomly but at specific sites in the genome during replication, the process of DNA making exact copies of itself before cell division.

RAD51 is a eukaryotic gene. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to the bacterial RecA, Archaeal RadA and yeast Rad51. The protein is highly conserved in most eukaryotes, from yeast to humans.

The RAD51 gene provides instructions for making a protein that is essential for repairing damaged DNA. Breaks in DNA can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division.

Abstract. Deleterious mutations in the RAD51C gene, which encodes a DNA double-strand break (DSB) repair protein, have been reported to confer high-penetrance susceptibility to both breast and ovarian cancer.

The DNA double-strand break (DSB) is the principle cytotoxic lesion for ionizing radiation and radio-mimetic chemicals but can also be caused by mechanical stress on chromosomes or when a replicative DNA polymerase encounters a DNA single-strand break or other type of DNA lesion.