Related Experiment Video

Updated: Dec 13, 2025

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.0K

Structural insight into FANCI-FANCD2 monoubiquitination

Landing Li1,2, Winnie Tan1,2, Andrew J Deans1,2

  • 1Genome Stability Unit, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.

Essays in Biochemistry
|July 30, 2020
PubMed

Insights

Recent structural studies reveal how Fanconi anemia (FA) pathway proteins FANCD2 and FANCI are activated for DNA repair. This advances understanding of FA bone marrow failure syndrome and its molecular regulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Structural Biology

Background:

  • The Fanconi anemia (FA) pathway is crucial for repairing DNA damage, particularly interstrand cross-links, that impede DNA replication.
  • A central event in the FA pathway is the monoubiquitination of FANCD2 and FANCI proteins by the FA core complex, a large E3 ubiquitin ligase.
  • Defects in FA pathway components lead to Fanconi anemia, a bone marrow failure syndrome, highlighting the pathway's importance in human health.

Purpose of the Study:

  • To review recent advances in the structural and molecular understanding of key Fanconi anemia pathway components.
  • To elucidate the mechanisms of FANCD2 and FANCI monoubiquitination and their role in DNA repair.
  • To compare the activation steps of FANCD2 and FANCI monoubiquitination and explore regulatory mechanisms.

Main Methods:

  • Integration of recent cryo-electron microscopy (cryo-EM) studies for structural characterization of FA pathway proteins.
  • Incorporation of new biochemical studies to understand protein interactions and functional mechanisms.
  • Comparative analysis of structural and biochemical data to infer molecular mechanisms.

Main Results:

  • Recent cryo-EM and biochemical studies have significantly advanced the structural characterization of the FA core complex, FANCD2, and FANCI.
  • These studies provide detailed insights into the process of FANCD2 and FANCI monoubiquitination, a critical step for DNA repair.
  • The findings offer a more comprehensive molecular understanding of how these proteins function within the FA pathway.

Conclusions:

  • Recent structural and biochemical breakthroughs have greatly enhanced our understanding of the Fanconi anemia pathway's core components.
  • The detailed molecular insights into FANCD2/FANCI monoubiquitination and activation provide a foundation for understanding DNA repair mechanisms.
  • Further research into the regulation of these processes is crucial for comprehending Fanconi anemia pathogenesis and developing therapeutic strategies.
Keywords:
DNA synthesis and repairFanconi anemiabiochemistryenzyme activityprotein structureubiquitin ligases

More Related Videos

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

11.2K
In Vitro Analysis of E3 Ubiquitin Ligase Function06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

5.8K

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.4K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.8K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.2K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.5K
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
6.5K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.8K