Rpd3 regulates single-copy origins independently of the rDNA array by opposing origin stimulation by Fkh1 [ChIP-seq]

The replication of eukaryotic genomes is highly regulated to ensure faithful transmission of all genetic information through cell divisions. In addition to stringent control of origin initiation by cell cycle controls and DNA damage checkpoints, spatial and temporal control of origins serves to stage and balance replication of different genomic regions, with potential implications for development and genome stability. Replication of highly repetitive sequences creates stressful competition between genomic regions for sufficient replication resources. Here, we examined histone deacetylases Rpd3 and Sir2 in balancing replication between unique sequences and the multi-copy ribosomal DNA gene cluster(s), which has emerged as an evolutionarily conserved node of genomic instability. We elucidate Rpd3's mechanism of origin regulation, which is distinct and independent of Sir2.真核生物基因组的复制过程受到高度调控，以确保所有遗传信息可通过细胞分裂实现精准传递。除了通过细胞周期调控与DNA损伤检查点对复制起始位点的启动进行严格管控之外，对复制起始位点的时空调控还可对不同基因组区域的复制进行时序规划并平衡其复制进程，这对生物体发育与基因组稳定性具有潜在影响。高度重复序列的复制会在基因组各区域间催生针对充足复制资源的竞争性压力。本研究针对组蛋白去乙酰化酶Rpd3与Sir2展开探究，解析二者在独特序列与多拷贝核糖体DNA（ribosomal DNA, rDNA）基因簇之间平衡复制的机制——该基因簇已被证实为进化上保守的基因组不稳定节点。我们阐明了Rpd3调控复制起始位点的具体机制，该机制独立于Sir2且与Sir2的调控路径截然不同。