BMAL (ARNTL), CLOCK, 和 NPAS2 的表达
中文名称
通路描述
BMAL1 (ARNTL), CLOCK, 和 NPAS2 在昼夜节律基因表达中起冗余激活作用（参考 Cox 和 Takahashi, 2019）。它们的表达受 RORA、RORB 和 RORC 的正向调控，并受 NR1D1 (REV-ERBA) 的负向调控，这些受体均识别相同的 ROR 响应元件（RRE, RORE），该机制在 BMAL1 和 CLOCK 启动子中推断自小鼠同源物（Ueda 等，2002; Guilaumond 等，2005; Sato 等，2004; Akashi 和 Takumi 等，2005; Guillaumond 等，2005; Takeda 等，2012）。ROR 核受体结合氧化固醇（Wang 等，2010），而 NR1D1 结合血红素（Yin 等，2007; Raghuram 等，2007），从而与代谢提供潜在联系。ROR 核受体招募转录共激活因子如 EP300 (p300)、PPARGC1A (PGC1A)（推断自小鼠同源物 Lau 等，2004）和 NRIP1 (Poliandri 等，2011) 以通过 RNA 聚合酶 II 激活转录。相比之下，血红素结合的 NR1D1 招募核心抑制因子 NCOR1 和组蛋白去乙酰化酶 HDAC3 来抑制转录（Wu 等，2009）。编码 RORA、RORC 和 NR1D1 的基因受 BMAL1 和 CLOCK 调节，而 BMAL1 和 CLOCK 又受这些基因调节，从而构成哺乳动物昼夜节律中的次级环路。
英文描述
Resolution of D-loop Structures through Holliday Junction Intermediates D-loops generated after strand invasion and DNA repair synthesis during homologous recombination repair (HRR) can be resolved through Holliday junction intermediates.A D-loop can be cleaved by the complex of MUS81 and EME1 (MUS81:EME1) or MUS81 and EME2 (MUS81:EME2) and resolved without the formation of double Holliday junctions, generating cross-over products. All steps involved in this process have not been elucidated (Osman et al. 2003, Schwartz et al. 2012, Pepe and West 2014).Alternatively, double Holliday junctions can be created by ligation of crossed-strand intermediates. Double Holliday junctions can then be resolved through the action of the BLM helicase complex known as BTRR (BLM:TOP3A:RMI1:RMI2) (Wan et al. 2013, Bocquet et al. 2014). BLM-mediated resolution of Holliday junction intermediates prevents sister chromatid exchange (SCE) between mitotic chromosomes and generates non-crossover products. SPIDR enables recruitment of the BTTR complex to the ionizing radiation-induced foci. The complex of FIGNL1 and FIRRM, which, through FIGNL1, simultaneously interacts with SPIDR (Yuan and Chen 2013) and RAD51 (Yuan and Chen 2013, Fernandes et al. 2018), may facilitate the function of SPIDR in promoting the no cross-over route of homologous recombination repair. Mitotic SCE can result in the loss-of-heterozygosity (LOH), which can make the cell homozygous for deleterious recessive mutations (e.g. in tumor suppressor genes) (Wu and Hickson 2003). Double Holliday junctions can also be resolved by cleavage, mediated by GEN1 or the SLX-MUS complex (composed of SLX1A:SLX4 heterodimer and a heterodimer of MUS81 and EME1 or, possibly, EME2). The resolvase activity of GEN1 and SLX-MUS predominantly results in crossover products, with SCE (Fekairi et al. 2009, Wyatt et al. 2013, Sarbajna et al. 2014).
所含基因
34 个基因