Data from: Two subunits of human ORC are dispensable for DNA replication and proliferation

The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication

六亚基起始识别复合物（Origin Recognition Complex, ORC）被认为是真核生物中一类必需的ATP酶，它以环状异六聚体的形式结合复制起点，进而加载MCM2-7复合物并启动DNA复制。我们发现，在体外培养的人类细胞系中，当ORC2或ATP酶亚基ORC1的两个等位基因均被破坏后，细胞仍可借助完整的染色体复制起点进行增殖。敲除ORC1或ORC2的细胞，其染色质上MCM2-7的装载量降低，且存活与DNA复制过程会严格依赖于另一类ATP酶CDC6。由此可见，要么是缺少单个亚基（哪怕是其ATP酶亚基）的ORC环状复合物，可与CDC6协同加载足量的MCM2-7以启动DNA复制；要么细胞存在不依赖ORC但依赖CDC6的机制，可在复制起点上完成MCM2-7的装载。