Brandsma Inger, Gent Dik C
Department of Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Genome Integr. 2012 Nov 27;3(1):9. doi: 10.1186/2041-9414-3-9.
Proper repair of DNA double strand breaks (DSBs) is vital for the preservation of genomic integrity. There are two main pathways that repair DSBs, Homologous recombination (HR) and Non-homologous end-joining (NHEJ). HR is restricted to the S and G2 phases of the cell cycle due to the requirement for the sister chromatid as a template, while NHEJ is active throughout the cell cycle and does not rely on a template. The balance between both pathways is essential for genome stability and numerous assays have been developed to measure the efficiency of the two pathways. Several proteins are known to affect the balance between HR and NHEJ and the complexity of the break also plays a role. In this review we describe several repair assays to determine the efficiencies of both pathways. We discuss how disturbance of the balance between HR and NHEJ can lead to disease, but also how it can be exploited for cancer treatment.
正确修复DNA双链断裂(DSB)对于维持基因组完整性至关重要。修复DSB主要有两条途径,即同源重组(HR)和非同源末端连接(NHEJ)。由于需要姐妹染色单体作为模板,HR仅限于细胞周期的S期和G2期,而NHEJ在整个细胞周期都有活性且不依赖模板。这两条途径之间的平衡对于基因组稳定性至关重要,并且已经开发了许多测定方法来测量这两条途径的效率。已知几种蛋白质会影响HR和NHEJ之间的平衡,断裂的复杂性也起作用。在这篇综述中,我们描述了几种修复测定方法以确定这两条途径的效率。我们讨论了HR和NHEJ之间平衡的紊乱如何导致疾病,以及如何将其用于癌症治疗。