Related Experiment Video
Updated: Feb 4, 2026
04:17
DNA Virus Detection System Based on RPA-CRISPR/Cas12a-SPM and Deep Learning
Published on: May 10, 2024
1.6K
RPA-independent activation of the ATR/CHK1 pathway
Min Huang1, Dandan Zhu1, Junjie Chen1
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Summary
Replication protein A (RPA) typically activates the ATR/CHK1 pathway. This study reveals RPA-independent ATR/CHK1 activation upon RPA2 depletion, uncovering a dual mechanism for genome stability during replication stress.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- The ATR/CHK1 pathway is vital for genome stability during replication stress.
- Replication protein A (RPA) is traditionally considered essential for ATR signaling.
- RPA coats single-stranded DNA at stalled replication forks, recruiting ATR-ATRIP.
Purpose of the Study:
- To investigate the role of RPA in ATR/CHK1 pathway activation.
- To explore alternative mechanisms of ATR/CHK1 activation under replication stress.
- To uncover novel pathways regulating genome stability.
Main Methods:
- Utilized an inducible RPA2-dTAG degron system in 293A and RPE-1 cells.
- Assessed CHK1 phosphorylation (Ser296 and Ser345) via Western blotting.
- Employed ATR inhibition and analyzed the requirement for RAD9 and TOPBP1.
Main Results:
- Acute depletion of RPA2 induced robust ATR/CHK1 activation independently of RPA.
- Elevated CHK1 phosphorylation was ATR-dependent and abolished by ATR inhibition.
- RPA-independent activation necessitated checkpoint mediators RAD9 and TOPBP1.
Conclusions:
- Dual mechanisms (RPA-dependent and -independent) activate the ATR/CHK1 pathway.
- This RPA-independent pathway provides a backup for genome integrity under replication stress.
- The findings reveal a flexible replication stress response network crucial for preserving genomic stability.
Related Concept Videos
02:37Restarting Stalled Replication Forks
6.4K
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,...
6.4K
01:21Introduction to Test of Independence
3.0K
In statistics, the term independence means that one can directly obtain the probability of any event involving both variables by multiplying their individual probabilities. Tests of independence are chi-square tests involving the use of a contingency table of observed (data) values.
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
3.0K
01:16Hypothesis Test for Test of Independence
8.2K
The test of independence is a chi-square-based test used to determine whether two variables or factors are independent or dependent. This hypothesis test is used to examine the independence of the variables. One can construct two qualitative survey questions or experiments based on the variables in a contingency table. The goal is to see if the two variables are unrelated (independent) or related (dependent). The null and alternative hypotheses for this test are:
H0: The two variables (factors)...
H0: The two variables (factors)...
8.2K
02:03Law of Independent Assortment
62.7K
While Mendel’s Law of Segregation states that the two alleles for one gene are separated into different gametes, a different question of how different genes are inherited remains. For example, is the gene for tall plants inherited with the gene for green peas? Mendel asked this question by experimenting with a dihybrid cross; a cross in which both parents are homozygous for two distinct traits resulting in an F1 generation that are heterozygous for both traits.
62.7K
01:18Independent and Dependent Sources
2.6K
In electrical circuits, sources play a crucial role in providing power for the operation of the circuit. These sources can be broadly categorized into two types: independent and dependent.
Independent voltage or current sources supply a fixed amount of voltage or current, respectively, which is unaffected by other elements within the circuit. These are represented using specific symbols. Independent voltage sources are symbolized with polarities (+ and -), indicating the direction of the...
Independent voltage or current sources supply a fixed amount of voltage or current, respectively, which is unaffected by other elements within the circuit. These are represented using specific symbols. Independent voltage sources are symbolized with polarities (+ and -), indicating the direction of the...
2.6K
01:27C4 Pathway and CAM
49.2K
Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
C4 Pathway
The C4 pathway is used by plants such as...
49.2K