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DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

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...

DNA Damage Can Stall the Cell Cycle

DNA Damage Can Stall the Cell Cycle

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...

Restarting Stalled Replication Forks

Restarting Stalled Replication Forks

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,...

Translesion DNA Polymerases

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...

Homologous Recombination

Homologous Recombination

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...

Long-patch Base Excision Repair

Long-patch Base Excision Repair

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:

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相关实验视频

Updated: Jan 13, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

取决于DNA损伤的异形切换调节RIF1 DNA修复复合体组装和相位分离.

Adenine Si-Hui Koo¹, Weiyan Jia¹, Sang Hwa Kim¹

¹Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

The Journal of biological chemistry

|January 6, 2026

概括

此摘要是机器生成的。

RAP1交互因子1 (RIF1) 替代拼接产生不同的RIF1异型 (RIF1-L和RIF1-S),使其在DNA修复和基因组保护中的作用多样化. DNA损伤促进RIF1-S,影响蛋白质功能.

关键词:

造成的DNA损伤是DNA损伤.在MDC1中,MDC1是MDC1.在 RIF1 中, RIF1 是 RIF1 的一个类型.这是一种RNA结合蛋白.替代性拼接是一种替代性的拼接.细胞信号传递是细胞的信号传递.在这种情况下,染色染色素

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Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

相关实验视频

Last Updated: Jan 13, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

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:

蛋白质RAP1相互作用因子1 (RIF1) 在DNA双链断裂修复,DNA复制和核组织中起着至关重要的作用.
人们对RIF1执行其多种功能的确切机制仍然不完全了解.

研究的目的:

调查RIF1的替代拼接如何有助于其功能多样化.
阐明RIF1异型在对DNA损伤的反应中的作用及其在癌症中的含义.

主要方法:

分析RIF1中的替代拼接事件,重点关注C端域 (CTD) 中的磁带外子 (Ex32).
识别调控RIF1替代拼接的拼接因素 (SRSF1,SRSF3,SRSF7). 选择性的拼接.
异形特异性蛋白质组分析以确定RIF1-L和RIF1-S之间的结合伙伴和功能差异.
调查RIF1 CTD相分离活动和染色质保留动态.

主要成果:

RIF1 Ex32的替代拼接产生具有独特功能特征的RIF1-长 (RIF1-L) 和RIF1-短 (RIF1-S) 异型.
DNA损伤抑制了Ex32拼接,增加了RIF1-S表达,这种现象在原发性癌症中观察到.
RIF1-L优先与DNA损伤检查点1 (MDC1) 的调解器结合,并增强MDC1的焦点形成.
在RIF1-L中的富含Ser/Lys的磁带稳定了CTD相分离活性,并增强了通过CDK1酸化调节的染色质保留.

结论:

RIF1的DNA损伤依赖的替代拼接是功能多样化的关键机制.
RIF1异型在基因组保护中发挥着独特的作用,其中RIF1-L有助于DNA损伤反应,而RIF1-S可能与癌症进展有关.
这些发现为RIF1调控及其在维护基因组完整性方面的多方面的作用提供了新的见解.