the relationship between the roles of brca genes in dna repair and cancer predisposition
BRCA1 BRCA1 and BRCA2 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks.[10][11] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.[12][13] BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominate allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer.[14]
Nucleotide excision repair The process of nucleotide excision repair is controlled in Escherichia coli by the UvrABC endonuclease enzyme complex, which consists of four Uvr proteins: UvrA, UvrB, UvrC, and DNA helicase II (sometimes also known as UvrD in this complex). First, a UvrA-UvrB complex scans the DNA, with the UvrA subunit recognizing distortions in the helix, caused for example by pyrimidine dimers. When the complex recognizes such a distortion, the UvrA subunit leaves and an UvrC protein comes in and binds to the UvrB monomer and, hence, forms a new UvrBC dimer. UvrB cleaves a phosphodiester bond 4 nucleotides downstream of the DNA damage, and the UvrC cleaves a phosphodiester bond 8 nucleotides upstream of the DNA damage and created 12 nucleotide excised segment. DNA helicase II (sometimes called UvrD) then comes in and removes the excised segment by actively breaking the hydrogen bonds between the complementary bases. The resultant gap is then filled in using DNA polymerase I and DNA ligase. The basic excision process is very similar in higher cells, but these cells usually involve many more proteins â€“ E.coli is a simple example.[5]