MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Trends Biochem Sci. 2013 Sep;38(9):461-6. doi: 10.1016/j.tibs.2013.06.011. Epub 2013 Aug 1.
The regulation of chromatin structure is of paramount importance for a variety of fundamental nuclear processes, including gene expression, DNA repair, replication, and recombination. The ATP-dependent chromatin-remodelling factor ATRX (α thalassaemia/mental retardation X-linked) has emerged as a key player in each of these processes. Exciting recent developments suggest that ATRX plays a variety of key roles at tandem repeat sequences within the genome, including the deposition of a histone variant, prevention of replication fork stalling, and the suppression of a homologous recombination-based pathway of telomere maintenance. Here, we provide a mechanistic overview of the role of ATRX in each of these processes, and propose how they may be connected to give rise to seemingly disparate human diseases.
染色质结构的调节对于多种基本核过程至关重要,包括基因表达、DNA 修复、复制和重组。ATP 依赖性染色质重塑因子 ATRX(α-地中海贫血/智力迟钝 X 连锁)已成为这些过程中的关键参与者。令人兴奋的最新发展表明,ATRX 在基因组内的串联重复序列中发挥多种关键作用,包括组蛋白变体的沉积、防止复制叉停滞以及抑制基于同源重组的端粒维持途径。在这里,我们提供了 ATRX 在这些过程中的作用的机制概述,并提出了它们如何连接起来导致看似不同的人类疾病。