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An Essential and Cell-Cycle-Dependent ORC Dimerization Cycle Regulates Eukaryotic Chromosomal DNA Replication.

Abstract：

:Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), completing replication licensing. However, how an asymmetric single-heterohexameric ORC structure loads the symmetric MCM (minichromosome maintenance) double hexamers is controversial, and importantly, it remains unknown when and how ORC proteins associate with the newly replicated origins to protect them from invasion by histones. Here, we report an essential and cell-cycle-dependent ORC "dimerization cycle" that plays three fundamental roles in the regulation of DNA replication: providing a symmetric platform to load the symmetric pre-RCs, marking and protecting the nascent sister replication origins for the next licensing, and playing a crucial role to prevent origin re-licensing within the same cell cycle.

journal_name

Cell Rep

journal_title

Cell reports

authors

Amin A,Wu R,Cheung MH,Scott JF,Wang Z,Zhou Z,Liu C,Zhu G,Wong CK,Yu Z,Liang C

doi

10.1016/j.celrep.2020.02.046

subject

Has Abstract

pub_date

2020-03-10 00:00:00

pages

3323-3338.e6

issue

10

issn

2211-1247

pii

S2211-1247(20)30207-2

journal_volume

30

pub_type

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