OTUD5通过组织染色体重塑剂来限制复制叉的不稳定性
Angelo de Vivo1, Hongseon Song2, Yujin Lee2
1Department of Molecular Biosciences, College of Arts and Sciences, University of South Florida, Tampa, FL 33647, USA.
Nucleic acids research
|September 15, 2023
概括
杜比基因酶OTUD5通过组织一个包括FACT和HDAC1/2.2.在内的复合体来限制复制应激. 这种相互作用防止了过度的FACT负载和R循环形成,保持了基因组的稳定性.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- 复制叉的进展对于基因组的维护至关重要.
- 转录复制冲突可以破坏复制分叉的稳定性.
- 染色体重塑剂调节复制应激,但它们的组织不清楚.
研究的目的:
- 研究OTUD5在调节复制应激中的作用.
- 确定OTUD5限制复制应激的蛋白质复合体和机制.
主要方法:
- 招募对复制分叉进行测试.
- 对复制叉压力标记物的分析.
- 细胞系的工程,以解蛋白相互作用.
- 蛋白质组分析和通路激活研究.
主要成果:
- OTUD5被招募到复制叉,其耗尽导致压力.
- OTUD5通过其C端尾部组装了FACT,HDAC1和HDAC2的复合体.
- 破坏OTUD5-FACT相互作用会增加FACT负载,R循环形成和复制压力.
- OTUD5 招募 HDAC1/2 以减少 H4K16 乙化和 FACT 招募.
- OTUD5 缺乏激活了Fanconi 贫血细胞生存途径.
结论:
- OTUD5在限制转录诱导的复制压力方面发挥着新的作用.
- 确定了一个新的交互网络,涉及OTUD5,FACT,HDAC1和HDAC2.
- 这种网络对于保持复制分叉的完整性至关重要.
相关概念视频
Restarting Stalled Replication Forks
5.8K
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,...
5.8K
The DNA Replication Fork
36.1K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
36.1K
Replication in Eukaryotes
13.9K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.9K
Nucleosome Remodeling
9.2K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.2K
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
The Replisome
33.6K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
33.6K


