容易发生错误的,压力诱导的基于3'片的Okazaki片段成熟支持细胞存活
Haitao Sun1, Zhaoning Lu1, Amanpreet Singh1
1Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
概括
具有DNA复制缺陷的细胞在压力下激活易发生错误的Okazaki片段成熟路径. 这种途径会产生突变,如内部合复制,使细胞能够生存和进化.
科学领域:
- 分子生物学
- 遗传学
- 细胞生物学
背景情况:
- 具有DNA复制缺陷的细胞通常在环境压力下面临亡.
- 了解这些细胞获得突变的机制对于生存至关重要.
研究的目的:
- 研究在压力下DNA复制缺陷的酵母细胞中Okazaki片段成熟 (OFM) 途径的激活.
- 确定这种途径产生的特定突变及其在细胞生存中的作用.
主要方法:
- 使用的rad27Δ酵母细胞受到限制性温度应激.
- 分析了Dun1激酶的激活和3′核酶的作用,包括DNA聚合酶 δ (Polδ).
- 研究了3′片中的二次结构的形成和随后的DNA扩展.
主要成果:
- 在限制性温度下,在rad27Δ酵母细胞中激活了由压力诱导的易发生错误的OFM通路.
- 这种途径导致了具有短间距序列的替代重复的形成,例如pol3内部合重复.
- 产生的突变抑制了通常由rad27Δ在压力下诱导的致命性.
结论:
- 定义了一个新型的压力诱导,容易出错的OFM路径.
- 这种途径产生特定的突变,抵消复制缺陷,促进细胞进化和生存.
- 提供关于细胞如何在具有挑战性的环境条件下适应和生存的见解.
相关概念视频
Restarting Stalled Replication Forks
6.0K
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,...
6.0K
DNA Damage can Stall the Cell Cycle
9.5K
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...
9.5K
The DNA Replication Fork
37.6K
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...
37.6K
Long-patch Base Excision Repair
7.3K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.3K
Nonsense-mediated mRNA Decay
11.0K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.0K
Nuclear Export of mRNA
7.9K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K


