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]
Histone acetylation and deacetylation Acetylation has the effect of changing the overall charge of the histone tail from positive to neutral. Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A histone fold domains. Acetylation of the histone tails disrupts this association, leading to weaker binding of the nucleosomal components.[1] By doing this, the DNA is more accessible and leads to more transcription factors being able to reach the DNA. Thus, acetylation of histones is known to increase the expression of genes through transcription activation. Deacetylation performed by HDAC molecules has the opposite effect. By deacetylating the histone tails, the DNA becomes more tightly wrapped around the histone cores, making it harder for transcription factors to bind to the DNA. This leads to decreased levels of gene expression and is known as gene silencing.[5][6][7]