通过受损染色体结构域的聚集揭示的DNA双链断裂动态

Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains.

作者信息

Aten Jacob A, Stap Jan, Krawczyk Przemek M, van Oven Carel H, Hoebe Ron A, Essers Jeroen, Kanaar Roland

机构信息

Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, Netherlands.

出版信息

Science. 2004 Jan 2;303(5654):92-5. doi: 10.1126/science.1088845.

DOI:10.1126/science.1088845

PMID:14704429

Abstract

Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, the static "contact-first" and the dynamic "breakage-first" theory, differ fundamentally in their requirement for DSB mobility. To determine whether or not DSB-containing chromosome domains are mobile and can interact, we introduced linear tracks of DSBs in nuclei. We observed changes in track morphology within minutes after DSB induction, indicating movement of the domains. In a subpopulation of cells, the domains clustered. Juxtaposition of different DSB-containing chromosome domains through clustering, which was most extensive in G1 phase cells, suggests an adhesion process in which we implicate the Mre11 complex. Our results support the breakage-first theory to explain the origin of chromosomal translocations.

摘要

来自不同DNA双链断裂（DSB）的末端之间的相互作用可产生致瘤性染色体易位。关于易位中DSB并列的两种理论，即静态的“接触优先”和动态的“断裂优先”理论，在对DSB移动性的要求上存在根本差异。为了确定含DSB的染色体结构域是否可移动并能相互作用，我们在细胞核中引入了DSB的线性轨迹。我们观察到DSB诱导后几分钟内轨迹形态发生了变化，表明这些结构域发生了移动。在一部分细胞中，这些结构域聚集在一起。通过聚集使不同的含DSB染色体结构域并列，这在G1期细胞中最为广泛，提示了一个我们认为涉及Mre11复合体的黏附过程。我们的结果支持断裂优先理论来解释染色体易位的起源。