Nature Genetics：DNA断裂发生的概率极低但危险性大

irisln

Nature Genetics：DNA断裂发生的概率极低但危险性大 复制诱导的DNA断裂是一个自发过程，有可能是染色体重组引起癌症的主要起因。但是，在正常细胞中，这个过程的发生概率有多大还不清楚。一项新的研究表明，这个过程发生的概率非常低。然而，一旦发生，它对基因组稳定性的危害将是之前预计的100倍。
  生物谷报道：复制诱导的DNA断裂是一个自发过程，有可能是染色体重组引起癌症的主要起因。但是，在正常细胞中，这个过程的发生概率有多大还不清楚。一项新的研究表明，这个过程发生的概率非常低。然而，一旦发生，它对基因组稳定性的危害将是之前预计的100倍。

图：SOS-GFP分析图谱。
在大肠杆菌的环形基因组上，携带着复制起点oriC（左上图）。一旦复制启动（右上图），将形成两个复制叉（桔色的三角形）。其中的一个复制叉停滞了下来（右下图），并且发生瓦解（复制蛋白解体，从DNA上脱落下来，图中用空的三角形表示）。在瓦解的复制叉上会产生一个DSB，并由之诱导SOS DNA损伤反应。这个反应诱导转录从sulA开始（桔色的四边形），诱导gfp基因的表达。在诱导SOS反应后，大肠杆菌呈现绿色（左下图）。此时，细胞可以修复瓦解的复制叉，并继续进行复制。（引自生命经纬）
原始出处:
Nature Genetics 39, 797 - 802 (2007) Published online: 27 May 2007 | doi:10.1038/ng2051
Spontaneous DNA breakage in single living Escherichia coli cells
Jeanine M Pennington1 & Susan M Rosenberg1,2
Abstract
Spontaneous DNA breakage is predicted to be a frequent, inevitable consequence of DNA replication and is thought to underlie much of the genomic change that fuels cancer and evolution1, 2, 3. Despite its importance, there has been little direct measurement of the amounts, types, sources and fates of spontaneous DNA lesions in living cells. We present a direct, sensitive flow cytometric assay in single living Escherichia coli cells for DNA lesions capable of inducing the SOS DNA damage response, and we report its use in quantification of spontaneous DNA double-strand breaks (DSBs). We report efficient detection of single chromosomal DSBs and rates of spontaneous breakage

20- to 100-fold lower than predicted. In addition, we implicate DNA replication in the origin of spontaneous DSBs with the finding of fewer spontaneous DSBs in a mutant with altered DNA polymerase III. The data imply that spontaneous DSBs induce genomic changes and instability 20–100 times more potently than previously appreciated. Finally, FACS demonstrated two main cell fates after spontaneous DNA damage: viability with or without resumption of proliferation.
Interdepartmental Program in Cell and Molecular Biology and Department of Molecular and Human Genetics, Houston, Texas 77030-3411, USA.
Department of Biochemistry and Molecular Biology, Department of Molecular Virology and Microbiology and Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3411, USA.