Related Experiment Video
Updated: Aug 6, 2026
10:59
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
SUDS3 nuclear condensates decelerate DNA replication and safeguard genome stability
Zhifen Zhou1, Kunling Huang2, Ruofei Li3
1Innovative Center of Healthy Longevity and Synthetic Biology, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China; Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Cell Reports
|July 18, 2026
Summary
SUDS3 protein forms nuclear condensates that control DNA replication speed. Loss of SUDS3 causes accelerated replication forks, genome instability, and increased sensitivity to chemotherapy.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Precise control of DNA replication fork progression is crucial for maintaining genome integrity.
- Mechanisms that prevent excessive replication fork acceleration are not fully understood.
Purpose of the Study:
- To identify regulators of replication speed.
- To investigate the role of SUDS3 in controlling replication dynamics and genome stability.
Main Methods:
- Identification of SUDS3 as a condensate-associated regulator of replication speed.
- Analysis of SUDS3 condensate formation during S phase and replication stress.
- Assessment of replication fork progression, DNA single-strand accumulation, and genome instability in SUDS3-deficient cells.
- Evaluation of cellular sensitivity to chemotherapeutic agents.
Main Results:
- SUDS3 forms dynamic nuclear condensates that spatially partition replication factors like MCM10, limiting their chromatin accessibility.
- Loss of SUDS3 leads to aberrantly accelerated replication fork progression.
- SUDS3 deficiency results in defective fork protection, increased single-stranded DNA, ATR-CHK1 hyperactivation, and genome instability, particularly under replication stress.
- SUDS3-deficient cells exhibit increased sensitivity to replication-targeting chemotherapeutic agents, a phenotype rescued by wild-type SUDS3.
Conclusions:
- SUDS3 condensates provide a mechanism for constraining DNA replication dynamics.
- SUDS3 condensates are critical for safeguarding genome stability.
- SUDS3 condensates represent potential vulnerabilities in replication-stressed cancers.
Related Concept Videos
02:36DNA 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...
02:36DNA 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...
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:37Restarting 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, a...
01:02The DNA Replication Fork
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 forks, one in...