Densham Ruth M, Morris Joanna R
Birmingham Centre for Genome Biology, Institute of Cancer and Genomic Sciences, Medical and Dental Schools, University of Birmingham, Birmingham, United Kingdom.
Front Mol Biosci. 2019 Sep 3;6:79. doi: 10.3389/fmolb.2019.00079. eCollection 2019.
DNA double-strand breaks (DSBs) occur in our cells in the context of chromatin. This type of lesion is toxic, entirely preventing genome continuity and causing cell death or terminal arrest. Several repair mechanisms can act on DNA surrounding a DSB, only some of which carry a low risk of mutation, so that which repair process is utilized is critical to the stability of genetic material of cells. A key component of repair outcome is the degree of DNA resection directed to either side of the break site. This in turn determines the subsequent forms of repair in which DNA homology plays a part. Here we will focus on chromatin and chromatin-bound complexes which constitute the "mountains" that block resection, with a particular focus on how the breast and ovarian cancer predisposition protein-1 (BRCA1) contributes to repair outcomes through overcoming these blocks.
DNA双链断裂(DSBs)在我们细胞的染色质环境中发生。这种类型的损伤具有毒性,会完全破坏基因组的连续性并导致细胞死亡或终末停滞。几种修复机制可作用于双链断裂周围的DNA,其中只有一些携带低突变风险,因此采用哪种修复过程对细胞遗传物质的稳定性至关重要。修复结果的一个关键组成部分是指向断裂位点两侧的DNA切除程度。这反过来又决定了随后涉及DNA同源性的修复形式。在这里,我们将重点关注构成阻碍切除的“山脉”的染色质和与染色质结合的复合物,特别关注乳腺癌和卵巢癌易感蛋白1(BRCA1)如何通过克服这些障碍来促进修复结果。