London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, UK.
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, UK.
Trends Biochem Sci. 2014 Sep;39(9):409-19. doi: 10.1016/j.tibs.2014.07.003. Epub 2014 Aug 14.
Holliday junctions (HJs) are four-stranded DNA intermediates that arise during the recombinational repair of DNA double-strand breaks (DSBs). Their timely removal is crucial for faithful chromosome segregation and genome stability. In mammalian cells, HJs are processed by the BTR (BLM-topoisomerase IIIα-RMI1-RMI2) complex, the SLX-MUS (SLX1-SLX4-MUS81-EME1) complex, and the GEN1 resolvase. Recent studies have linked the deficiency of one or more of these enzymes to perturbed DNA replication, impaired crosslink repair, chromosomal instability, and defective mitoses, coupled with the transmission of widespread DNA damage and high levels of mortality. We review these key advances and how they have cemented the status of HJ-processing enzymes as guardians of genome integrity and viability in mammalian cells.
霍利迪连接点（HJs）是 DNA 双链断裂（DSBs）重组修复过程中产生的四链 DNA 中间体。它们的及时去除对于保证染色体正确分离和基因组稳定性至关重要。在哺乳动物细胞中，HJs 由 BTR（BLM-topoisomerase IIIα-RMI1-RMI2）复合物、SLX-MUS（SLX1-SLX4-MUS81-EME1）复合物和 GEN1 解旋酶处理。最近的研究将这些酶中的一种或多种的缺乏与 DNA 复制紊乱、交联修复受损、染色体不稳定和有缺陷的有丝分裂联系起来，同时伴随着广泛的 DNA 损伤和高死亡率的传递。我们回顾了这些关键进展，以及它们如何巩固了 HJ 加工酶作为哺乳动物细胞中基因组完整性和活力守护者的地位。
