Dynamic Interaction of Y RNAs with Chromatin and Initiation Proteins During Human DNA Replication

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2011 May 26

PMID 21610089

Citations 47

Authors

Alice Tianbu Zhang

Alexander R Langley

Christo P Christov

Eyemen Kheir

Thomas Shafee

Timothy J Gardiner

Torsten Krude

Affiliations

Soon will be listed here.

Abstract

Non-coding Y RNAs are required for the initiation of chromosomal DNA replication in mammalian cells. It is unknown how they perform this function or if they associate with a nuclear structure during DNA replication. Here, we investigate the association of Y RNAs with chromatin and their interaction with replication proteins during DNA replication in a human cell-free system. Our results show that fluorescently labelled Y RNAs associate with unreplicated euchromatin in late G1 phase cell nuclei before the initiation of DNA replication. Following initiation, Y RNAs are displaced locally from nascent and replicated DNA present in replication foci. In intact human cells, a substantial fraction of endogenous Y RNAs are associated with G1 phase nuclei, but not with G2 phase nuclei. Y RNAs interact and colocalise with the origin recognition complex (ORC), the pre-replication complex (pre-RC) protein Cdt1, and other proteins implicated in the initiation of DNA replication. These data support a molecular 'catch and release' mechanism for Y RNA function during the initiation of chromosomal DNA replication, which is consistent with Y RNAs acting as replication licensing factors.

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