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本文引用的文献

1
Equal sister chromatid exchange is a major mechanism of double-strand break repair in yeast.均等姐妹染色单体交换是酵母中双链断裂修复的主要机制。
Mol Cell. 2003 Jun;11(6):1661-71. doi: 10.1016/s1097-2765(03)00183-7.
2
Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre.多个DNA双链断裂在单个Rad52修复中心的共定位。
Nat Cell Biol. 2003 Jun;5(6):572-7. doi: 10.1038/ncb997.
3
Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability.在DNA复制过程中发挥作用的酿酒酵母染色质组装因子在基因组稳定性维持中起作用。
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6640-5. doi: 10.1073/pnas.1232239100. Epub 2003 May 15.
4
Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest.有缺陷的S期染色质组装会导致DNA损伤、S期检查点激活以及S期停滞。
Mol Cell. 2003 Feb;11(2):341-51. doi: 10.1016/s1097-2765(03)00037-6.
5
Defects in SPT16 or POB3 (yFACT) in Saccharomyces cerevisiae cause dependence on the Hir/Hpc pathway: polymerase passage may degrade chromatin structure.酿酒酵母中SPT16或POB3（yFACT）的缺陷导致对Hir/Hpc途径的依赖：聚合酶通过可能会破坏染色质结构。
Genetics. 2002 Dec;162(4):1557-71. doi: 10.1093/genetics/162.4.1557.
6
Histone H3 and the histone acetyltransferase Hat1p contribute to DNA double-strand break repair.组蛋白H3和组蛋白乙酰转移酶Hat1p有助于DNA双链断裂修复。
Mol Cell Biol. 2002 Dec;22(23):8353-65. doi: 10.1128/MCB.22.23.8353-8365.2002.
7
Maintenance of genome stability in Saccharomyces cerevisiae.酿酒酵母中基因组稳定性的维持。
Science. 2002 Jul 26;297(5581):552-7. doi: 10.1126/science.1075277.
8
Chromatin assembly. Cooperation between histone chaperones and ATP-dependent nucleosome remodeling machines.染色质组装。组蛋白伴侣与ATP依赖的核小体重塑机器之间的协作。
Eur J Biochem. 2002 May;269(9):2268-74. doi: 10.1046/j.1432-1033.2002.02890.x.
9
Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway.人类Asf1与CAF-1在修复偶联的核小体组装途径中相互作用并协同发挥作用。
EMBO Rep. 2002 Apr;3(4):329-34. doi: 10.1093/embo-reports/kvf068. Epub 2002 Mar 15.
10
Chromatin assembly factor I mutants defective for PCNA binding require Asf1/Hir proteins for silencing.对增殖细胞核抗原（PCNA）结合有缺陷的染色质组装因子I突变体在沉默过程中需要Asf1/Hir蛋白。
Mol Cell Biol. 2002 Jan;22(2):614-25. doi: 10.1128/MCB.22.2.614-625.2002.

酵母染色质组装因子Asf1的缺失会增加基因组不稳定性和姐妹染色单体交换。

The absence of the yeast chromatin assembly factor Asf1 increases genomic instability and sister chromatid exchange.

作者信息

Prado Félix, Cortés-Ledesma Felipe, Aguilera Andrés

机构信息

Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Avda. Reina Mercedes 6, 41012 Sevilla, Spain.

出版信息

EMBO Rep. 2004 May;5(5):497-502. doi: 10.1038/sj.embor.7400128. Epub 2004 Apr 8.

DOI:10.1038/sj.embor.7400128
PMID:15071494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1299049/
Abstract

Histone chaperone Asf1 participates in heterochromatin silencing, DNA repair and regulation of gene expression, and promotes the assembly of DNA into chromatin in vitro. To determine the influence of Asf1 on genetic stability, we have analysed the effect of asf1Delta on homologous recombination. In accordance with a defect in nucleosome assembly, asf1Delta leads to a loss of negative supercoiling in plasmids. Importantly, asf1Delta increases spontaneous recombination between inverted DNA sequences. This increase correlates with an accumulation of double-strand breaks (DSBs) as determined by immunodetection of phosphorylated histone H2A and fluorescent detection of Rad52-YFP foci during S and G2/M phases. In addition, asf1Delta shows high levels of sister chromatid exchange (SCE) and is proficient in DSB-induced SCE as determined by physical analysis. Our results suggest that defective chromatin assembly caused by asf1Delta leads to DSBs that can be repaired by SCE, affecting genetic stability.

摘要

组蛋白伴侣Asf1参与异染色质沉默、DNA修复和基因表达调控，并在体外促进DNA组装成染色质。为了确定Asf1对遗传稳定性的影响，我们分析了asf1Delta对同源重组的作用。与核小体组装缺陷一致，asf1Delta导致质粒中负超螺旋的丧失。重要的是，asf1Delta增加了反向DNA序列之间的自发重组。这种增加与双链断裂（DSB）的积累相关，这是通过在S期和G2/M期对磷酸化组蛋白H2A进行免疫检测以及对Rad52-YFP焦点进行荧光检测来确定的。此外，通过物理分析确定，asf1Delta显示出高水平的姐妹染色单体交换（SCE），并且在DSB诱导的SCE方面表现良好。我们的结果表明，asf1Delta导致的染色质组装缺陷会导致DSB，这些DSB可以通过SCE修复，从而影响遗传稳定性。