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Nucleosomes influence multiple steps during replication initiation

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Title
Nucleosomes influence multiple steps during replication initiation
Author(s)
Azmi, IF; Watanabe, S; Maloney, MF; Sukhyun Kang; Belsky, JA; MacAlpine, DM; Peterson, CL; Bell, SP
Publication Date
2017-03
Journal
ELIFE, v.6, no., pp.e22512 -
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
Abstract
Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation. Origin licensing assays showed that local nucleosome positioning enhanced origin specificity and modulated helicase loading by influencing ORC DNA binding. Interestingly, SWI/SNF- and RSC-remodeled nucleosomes were permissive for origin licensing but showed reduced helicase activation. Specific CREs rescued replication of these templates if added prior to helicase activation, indicating a permissive chromatin state must be established during origin licensing to allow efficient origin activation. Our studies show nucleosomes directly modulate origin licensing and activation through distinct mechanisms and provide insights into the regulation of replication initiation by chromatin. Copyright Azmi et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
URI
http://pr.ibs.re.kr/handle/8788114/4260
DOI
10.7554/eLife.22512
ISSN
2050-084X
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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