Related Experiment Video

Updated: Jul 17, 2026

The Lambda Select cII Mutation Detection System
07:08

The Lambda Select cII Mutation Detection System

Published on: April 26, 2018

Cdc7-Dbf4 and the human S checkpoint response to UVC

Timothy P Heffernan1, Keziban Ünsal-Kaçmaz2, Alexandra N Heinloth3

  • 1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.

The Journal of Biological Chemistry
|February 6, 2007
PubMed

Insights

The S checkpoint prevents DNA replication after UV damage. This study found Cdc7-Dbf4, not Cdc25A, is key in the UV response pathway, implicating Dbf4-dependent kinases.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • DNA Damage Response

Background:

  • The S checkpoint prevents DNA replication following UV damage, involving ATR and Chk1 kinases.
  • Downstream effectors of this UV-induced S checkpoint response remain poorly understood.

Purpose of the Study:

  • To investigate the downstream effectors of the UV-induced S checkpoint pathway that inhibits DNA replicon initiation.
  • To determine the roles of Cdc25A and the Cdc7-Dbf4 complex in this response.

Main Methods:

  • Utilized human cells exposed to sublethal and cytotoxic doses of UVC radiation.
  • Assessed Cdc25A protein levels and Cdk2-cyclin E kinase activity.
  • Examined interactions between Chk1, Cdc7, and Dbf4 using in vitro and in vivo assays.
  • Investigated the effect of Dbf4 overexpression on the S checkpoint response.

Main Results:

  • Cdc25A degradation and Cdk2-cyclin E inhibition were not intrinsic to the UVC-induced inhibition of replicon initiation at sublethal doses.
  • Cdc25A degradation occurred only at cytotoxic UVC fluences.
  • Dbf4 interacted with Cdc7 and was phosphorylated by Chk1 in vitro.
  • Dbf4 overexpression abrogated the S checkpoint response to UVC but not ionizing radiation.

Conclusions:

  • Cdc25A degradation and Cdk2-cyclin E inhibition are not early effectors of the UVC-induced S checkpoint.
  • The findings implicate a Dbf4-dependent kinase as a potential target in the ATR- and Chk1-dependent S checkpoint response to UVC radiation.

More Related Videos

Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant08:52

Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant

Published on: May 27, 2011

Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay05:55

Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay

Published on: August 23, 2024

Related Concept Videos

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...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...