Work

Origin recognition complex harbors an intrinsic nucleosome remodeling activity

Year: 2022

Type: article

Abstract: Eukaryotic DNA replication is initiated at multiple chromosomal sites known as origins of replication that are specifically recognized by the origin recognition complex (ORC) containing multiple ATPase sites. In budding yeast, ORC binds to specific DNA sequences known as autonomously replicating sequences (ARSs) that are mostly nucleosome depleted. However, nucleosomes may still inhibit the licensing of some origins by occluding ORC binding and subsequent MCM helicase loading. Using purified proteins and single-molecule visualization, we find here that the ORC can eject histones from a nucleosome in an ATP-dependent manner. The ORC selectively evicts H2A-H2B dimers but leaves the (H3-H4) 2 tetramer on DNA. It also discriminates canonical H2A from the H2A.Z variant, evicting the former while retaining the latter. Finally, the bromo-adjacent homology (BAH) domain of the Orc1 subunit is essential for ORC-mediated histone eviction. These findings suggest that the ORC is a bona fide nucleosome remodeler that functions to create a local chromatin environment optimal for origin activity.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2211568119

Authors: Sai Li, Michael R. Wasserman, Olga Yurieva, Lu Bai, Michael E. O’Donnell, Shixin Liu

Institutions: Rockefeller University, Howard Hughes Medical Institute, Pennsylvania State University

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences

Awards: G3035965227, Probing Symmetry Breaking in Epigenetic Inheritance: From Single Molecules to Systems Biology, Gene Regulation from Long-Distance Chromosomal Interactions in Yeast, Biochemical Mechanism and Structure of the Eukaryotic Replication Fork, Mechanism of chromatin accessibility, 3D chromosome organization, and their functions in gene regulation