文章基本信息

标题：SIR2 suppresses replication gaps and genome instability by balancing replication between repetitive and unique sequences
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作者：Eric J. Foss ; Uyen Lao ; Emily Dalrymple 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：3
页码：552-557
DOI：10.1073/pnas.1614781114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Replication gaps that persist into mitosis likely represent important threats to genome stability, but experimental identification of these gaps has proved challenging. We have developed a technique that allows us to explore the dynamics by which genome replication is completed before mitosis. Using this approach, we demonstrate that excessive allocation of replication resources to origins within repetitive regions, induced by SIR2 deletion, leads to persistent replication gaps and genome instability. Conversely, the weakening of replication origins in repetitive regions suppresses these gaps. Given known age- and cancer-associated changes in chromatin accessibility at repetitive sequences, we suggest that replication gaps resulting from misallocation of replication resources underlie age- and disease-associated genome instability.
关键词：SIR2 ; DNA replication ; repetitive sequences ; replication gaps ; ribosomal DNA