转录PBR循环在周心体重复时会通过Rad52依赖的ADR循环形成引起粗的染色体重排
Ran Xu1,2,3, Crystal Tang1, Jianfang N Wang1
1Department of Biological Sciences, Graduate School of Science, The University of Osaka, Toyonaka, Osaka 560-0043, Japan.
Nucleic acids research
|January 12, 2026
概括
异色染色素的损失会触发转录暂停-回溯-重新启动循环,形成R循环,通过Rad52介导的和复制导致DNA损伤和总体染色体重排 (GCRs). 这揭示了基因组不稳定的机制.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 由H3K9甲基化标记的异色染色素,通常会静止周心体重复并防止粗染色体重排 (GCRs).
- 转录导致在异性染色素损失时产生GCR的确切机制尚不完全理解.
研究的目的:
- 为了调查转录如何在没有异性染色素的情况下导致GCRs.
- 阐明R环和特定蛋白质在围心重复中介 GCR 的作用.
主要方法:
- 使用裂变酵母作为模型系统.
- 使用DNA-RNA免疫沉 (DRIP) 来检测R循环.
- 评估了包括clr4∆在内的各种突变菌株的GCR,并利用RNaseH1过度表达.
- 研究了Tfs1/TFIIS,Ubp3,Seb1,Rad52和Polδ在R循环形成和GCR中的作用.
- 进行了体外测试,以研究Rad52的活性.
主要成果:
- 丢失的异质色素 (Clr4) 导致了增加的 R-循环积累在周心重复.
- 已证明R环会导致GCRs,因为RNaseH1过度表达减少了两者.
- 涉及Tfs1/TFIIS,Ubp3和Seb1的转录暂停-回溯-重新启动 (PBR) 周期与基因毒性R循环形成有关.
- Rad52重组酶局限于周心体,并促进了GCRs,与受损的单链回火 (SSA) 减少了GCRs.
- 在实验室中,Rad52促进了化诱导的DNA-RNA循环 (ADR循环) 的形成,而Polδ参与了GCRs.
结论:
- 转录性PBR循环驱动R循环积累在异色染色素损失时的周心重复.
- 取决于Rad52的SSA将R循环转化为ADR循环,随后是Polδ依赖的断裂诱导复制 (BIR),导致同质介导的GCRs.
- 这项研究揭示了一种新的途径,该途径将异性染色质损失,转录,R循环和基因组不稳定性联系起来.
更多相关视频
07:55Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
Published on: September 11, 2022
2.2K
05:55Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication
Published on: August 23, 2024
1000
相关概念视频
02:37Restarting Stalled Replication Forks
6.3K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.3K
02:36DNA Damage can Stall the Cell Cycle
10.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.0K
02:36DNA Damage Can Stall the Cell Cycle
3.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
02:31Homologous Recombination
62.6K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
62.6K
02:04Fixing Double-strand Breaks
14.3K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
14.3K
02:04Polytene Chromosomes
10.9K
Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also...
10.9K