链接组素H1-BRCA1轴是复制叉稳定性的关键调解器
Meryem Ozgencil1, Arlinda Dullovi1, Romane Catherine Christiane Higos1
1Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Life science alliance
|June 26, 2023
概括
对基因组稳定性至关重要的是复制依赖的基因素H1变体. 它们的丧失损害了BRCA1的招募到停滞不前的复制分叉,导致分叉崩和细胞死亡.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 基因组完整性通过稳定DNA损伤期间的复制叉来维持.
- 复制分叉稳定和染色质环境之间的协调还不太清楚.
研究的目的:
- 调查复制依赖的基因组H1变异在协调基因组稳定性与染色质环境中的作用.
- 阐明在复制应激过程中基因组H1变体和BRCA1之间的相互作用.
主要方法:
- 在复制压力下研究了复制依赖的组分素H1变体和BRCA1之间的相互作用.
- 评估复制分叉的进展和稳定性在具有和没有基因组H1变异的细胞中.
- 研究了BRCA1对停滞的复制分叉的招募,使用氧尿素处理.
- 在缺乏细胞中分析了MRE11-依赖的分叉切除和崩.
主要成果:
- 复制依赖的基因组H1变体以复制压力依赖的方式与BRCA1相互作用.
- 组织素H1变体的丧失导致复制中间体停滞,BRCA1招募受损.
- 缺少基因组H1变异的细胞表现出MRE11依赖的分叉切除,崩,基因组不稳定性和细胞死亡.
结论:
- 复制依赖的基因组H1变体对于BRCA1依赖的复制分叉保护至关重要.
- 这些基因组变异在复制压力期间维持基因组稳定性方面发挥着关键作用.
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
36.2K
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...
36.2K
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
Homologous Recombination
50.7K
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...
50.7K
Histone Variants at the Centromere
4.4K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.4K
Replication in Eukaryotes
14.0K
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...
14.0K


