Related Experiment Video
Updated: May 15, 2026
07:09
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
DMAP1 is an essential regulator of ATM activity and function
1Mammalian Genetics Lab, Cancer Research UK, London Research Institute, London, UK.
Oncogene
|January 16, 2013
Summary
DNMT1-associated protein 1 (DMAP1) is crucial for activating the DNA damage kinase ATM, essential for genomic stability. DMAP1 regulates ATM signaling in response to DNA damage and hypotonic stress, impacting cellular repair mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- Ataxia telangiectasia (A-T) is an autosomal recessive disease linked to mutations in the ATM gene.
- ATM (Ataxia-Telangiectasia Mutated) kinase is central to DNA damage response and genomic stability.
- ATM activation is triggered by stimuli like ionizing radiation (IR) and hypotonic stress.
Purpose of the Study:
- To investigate the role of DMAP1 in ATM activation and signaling.
- To determine if DMAP1 is essential for ATM's response to different cellular stresses.
Main Methods:
- DMAP1 knockdown experiments to assess its impact on ATM activation.
- Analysis of ATM substrate phosphorylation and histone H4K16 acetylation.
- Evaluation of cellular responses like radiosensitivity and cell cycle checkpoints (G2/M).
Main Results:
- DMAP1 knockdown significantly impaired IR-induced ATM activation and G2/M checkpoint control, leading to radiosensitivity.
- DMAP1 is also essential for ATM signaling under hypotonic stress.
- DMAP1 depletion reduced H4K16 acetylation, a modification linked to chromatin relaxation and ATM activation.
- Overexpression of DMAP1 enhanced ATM signaling, indicating DMAP1 is a rate-limiting factor.
Conclusions:
- DMAP1 is a critical regulator of ATM activity, essential for its activation by DNA damage and hypotonic stress.
- DMAP1's role in modulating histone acetylation is key to its function in ATM signaling.
- Targeting DMAP1 may offer therapeutic strategies for A-T and other conditions involving DNA repair deficiencies.
Related Concept Videos
02:17Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
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...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:42Microtubule Associated Proteins (MAPs)
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...