A Dual Role for the Chromatin Reader ORCA/LRWD1 in Targeting the Origin Recognition Complex to Chromatin

ABSTRACT: Eukaryotic cells use chromatin marks to regulate the initiation of DNA replication. The Origin Recognition Complex (ORC)-associated protein ORCA plays a critical role in heterochromatin replication in mammalian cells by recruiting the initiator ORC, but the underlying mechanisms remain unclear. Here, we report crystal and cryo-electron microscopy structures of ORCA in complex with ORC's Orc2 subunit and nucleosomes, establishing that ORCA orchestrates ternary complex assembly by simultaneously recognizing a highly conserved peptide sequence in Orc2, nucleosomal DNA, and repressive histone trimethylation marks through an aromatic cage. Unexpectedly, binding of ORCA to nucleosomes prevents chromatin array compaction in a manner that relies on H4K20 trimethylation, a histone modification crit

SUBMITTER: Dr. Sumon Sahu 

PROVIDER: S-SCDT-10_15252-EMBJ_2023114654 | biostudies-other |

REPOSITORIES: biostudies-other