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Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
Restarting Stalled Replication Forks02:37

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, a...
DNA Damage can Stall the Cell Cycle02:36

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 Cycle02:36

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...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.

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Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications
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Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

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Function of TopBP1 in genome stability.

Miiko Sokka1, Sinikka Parkkinen, Helmut Pospiech

  • 1DNA Damage Response Laboratory, Biochemistry, School of Natural Sciences, National University of Ireland, Galway, Ireland.

Sub-Cellular Biochemistry
|December 17, 2009
PubMed
Summary

Human DNA topoisomerase IIbeta-binding protein 1 (TopBP1) is crucial for genomic integrity, activating ATR to manage DNA replication and stress. Its functions extend to transcription regulation in higher eukaryotes, impacting cell proliferation and apoptosis.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Human DNA topoisomerase IIbeta-binding protein 1 (TopBP1) and its orthologues are proteins with multiple BRCT modules.
  • These proteins interact with various proteins involved in nuclear processes, playing essential roles in maintaining genomic integrity.
  • TopBP1 is vital for activating ATM and Rad3-related (ATR), a key regulator of DNA replication and replication stress response.

Purpose of the Study:

  • To review recent research on the multiple cellular functions of TopBP1.
  • To focus on the functions of TopBP1 and its orthologues in metazoan systems.
  • To elucidate the roles of TopBP1 in DNA replication, DNA damage response, and transcription regulation.

Main Methods:

  • Literature review of recent progress in TopBP1 research.
  • Analysis of TopBP1's interactions with other proteins.
  • Comparative analysis of TopBP1 functions across different eukaryotic systems.

Main Results:

  • TopBP1 is essential for genomic integrity maintenance.
  • TopBP1 activates ATR, regulating DNA replication and replication stress response.
  • Orthologues are involved in DNA replication and damage response; higher eukaryotic proteins also regulate transcription, affecting proliferation, damage response, and apoptosis.

Conclusions:

  • TopBP1 possesses diverse functions essential for nuclear processes.
  • Its roles in DNA replication, damage response, and transcription are critical for cell survival and proliferation.
  • Further research on TopBP1 in metazoan systems is ongoing to fully understand its complex functions.