| Literature DB >> 28735753 |
Andres Canela1, Yaakov Maman1, Seolkyoung Jung2, Nancy Wong1, Elsa Callen1, Amanda Day1, Kyong-Rim Kieffer-Kwon2, Aleksandra Pekowska2, Hongliang Zhang3, Suhas S P Rao4, Su-Chen Huang5, Peter J Mckinnon6, Peter D Aplan7, Yves Pommier3, Erez Lieberman Aiden5, Rafael Casellas2, André Nussenzweig8.
Abstract
In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT. Published by Elsevier Inc.Entities:
Keywords: DNA breaks; breakpoint cluster regions; cancer; fragile sites; genome instability; topoisomerase; topologically associated domains; translocations
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Year: 2017 PMID： 28735753 PMCID： PMC6133249 DOI： 10.1016/j.cell.2017.06.034
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582