What is Warsaw breakage syndrome?

Warsaw breakage syndrome is a genetic disorder that causes multiple abnormalities due to the mutation in the DDX11 gene. The function of DDX11 is to guides the production of an enzyme called ChlR1 which primarily function as a helicase but the mechanism by which DDX11 acts in Warsaw breakage syndrome (WBS) remained unclear.

What’s New?

A new study led by the team of researchers from Tokyo Metropolitan University and the FIRC Institute of Molecular Oncology (IFOM) in Italy have discovered the unknown function of DDX11 gene. Researchers identified that DDX11 has a critical role in DNA repair and also act as a backup to the Fanconi Anemia (FA) pathway. FA pathway function is to guards the genome.

During their study, researchers examined the function of DDX11 in avian cells and they specifically noted the similarities in the cells of WABS patients to those of Fanconi Anemia (FA).

Why DDX11 So Important?

They also found that DDX11 have a major function in DNA repair. This gene act together with the 9-1-1 checkpoint to scan out the damaged DNA wide-range of bulky lesions. If there is any damage in DNA after replication, DDX11 gene helps in its repair. Additionally, it also acts as a backup of the FA pathway whose function is to guard the genome by repairing interstrand crosslinks which can lead to cell death and developmental problems.

This finding helps in understanding the connection between WABS and FA cells exposed to ICLs, which caused WABS to be classified as an FA-like disorder.

The researchers also discovered that DDX11 is involved in immunoglobulin-variable gene diversification, a key mechanism in the healthy function and adaptability of a healthy immune system. As immunoglobulin-variable gene diversification is induced by abasic sites, the most common endogenous lesion in mammalian cells, one implication is that DDX11 and 9-1-1 promote DNA damage tolerance of abasic sites, a finding that potentially explains the essential role of DDX11 and its similarity with 9-1-1 during development.

This study sheds light on the understanding of biological mechanism as well as helps to understand disorders begin from the cellular level.

These findings have profound medical significance for several conditions, including cancer and developmental disorders associated with DNA repair deficiency.