Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.245076v1?rss=1 Authors: Shibata, E., Dutta, A. Abstract: The six-subunit Origin Recognition Complex (ORC) binds to origins of replication as a ring-shaped heterohexameric ATPase that is essential to recruit MCM2-7 and initiate DNA replication. We now report that human HCT116 colon cancer cells survive with a mutation in the initiator ATG of the ORC5 gene that abolishes the expression of ORC5 protein. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2-7 and initiate replication from similar number of origins as wild type cells. A second mutation in ORC2 in ORC5 mutant cells rendered both ORC5 and ORC2 proteins undetectable, and yet the cells grow, recruit MCM2-7 normally to chromatin and initiate DNA replication with similar number of origins. Thus, either a crippled ORC lacking ORC2 and ORC5 can load MCM2-7 to initiate DNA replication, or human cell-lines can recruit MCM2-7 to origins in a reaction independent of ORC. Copy rights belong to original authors. Visit the link for more info