School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Génétique, Reproduction et Développement, Faculté de Médecine, UMR CNRS 6293-INSERM U1103-Université Clermont Auvergne, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.
Int J Mol Sci. 2021 Dec 4;22(23):13115. doi: 10.3390/ijms222313115.
DNA entanglements and supercoiling arise frequently during normal DNA metabolism. DNA topoisomerases are highly conserved enzymes that resolve the topological problems that these structures create. Topoisomerase II (TOPII) releases topological stress in DNA by removing DNA supercoils through breaking the two DNA strands, passing a DNA duplex through the break and religating the broken strands. TOPII performs key DNA metabolic roles essential for DNA replication, chromosome condensation, heterochromatin metabolism, telomere disentanglement, centromere decatenation, transmission of crossover (CO) interference, interlock resolution and chromosome segregation in several model organisms. In this study, we reveal the endogenous role of TOPII in normal root growth and cell cycle, and mitotic DNA repair via homologous recombination. Additionally, we show that the protein is required for meiotic DSB repair progression, but not for CO formation. We propose that TOPII might promote mitotic HR DNA repair by relieving stress needed for HR strand invasion and D-loop formation.
在正常的 DNA 代谢过程中,DNA 经常会出现缠绕和超螺旋现象。DNA 拓扑异构酶是高度保守的酶,可以解决这些结构产生的拓扑问题。拓扑异构酶 II(TOPII)通过切断两条 DNA 链、使 DNA 双链穿过断裂点并重新连接断裂的链,从而消除 DNA 超螺旋,释放 DNA 中的拓扑应力。TOPII 在 DNA 复制、染色体浓缩、异染色质代谢、端粒解缠绕、着丝粒解连环、交叉(CO)干扰的传递、连锁的解决以及几种模式生物的染色体分离等关键的 DNA 代谢过程中发挥作用。在这项研究中,我们揭示了 TOPII 在正常根生长和细胞周期以及有丝分裂同源重组修复中的内源性作用。此外,我们还表明该蛋白对于减数分裂双链断裂修复的进展是必需的,但对于 CO 的形成则不是必需的。我们提出,TOPII 可能通过缓解 HR 链入侵和 D 环形成所需的压力来促进有丝分裂 HR DNA 修复。