Double strand breaks are also generated during repair of DNA cross links. By repairing DNA, these proteins play a role in maintaining the stability of the human genome and prevent dangerous gene rearrangements that can lead to hematologic and other cancers. BRCA2 has been shown to possess a crucial role in protection from the MRE11-dependent nucleolytic degradation of the reversed forks that are forming during DNA replication fork stalling (caused by obstacles such as mutations, intercalating agents etc.). Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development. Clinical significance Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast–ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal, and does not function properly. Researchers believe that the defective BRCA2 protein is unable to fix DNA damage that occurs throughout the genome. As a result, there is an increase in mutations due to error-prone translesion synthesis past un-repaired DNA damage, and some of these mutations can cause cells to divide in an uncontrolled way and form a tumor. People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression (reduced blood cell production that leads to anemia). Women having inherited a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1- and BRCA2-associated hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation, or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to carcinogens and an infectious process. An innate genomic deficit