Date Published: February 29, 2012
Publisher: Impact Journals LLC
Author(s): Mattia Frontini, Luca Proietti-De-Santis.
The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in triggering senescence and apoptosis and suppressing tumorigenesis. Although p53 is very important to avoid cancer, its excessive activity can be detrimental for the lifespan of the organism. This is why a network of positive and negative feedback loops, which most likely evolved to fine-tune the activity of this tumor suppressor, modulate its induction and activation. Accordingly, an unbalanced p53 activity gives rise to premature aging or cancer.
CSB is a 168 kDa protein that belongs to the SWI/SNF family of chromatin remodelers . It exhibits ATPase activity [2-4] and has conserved helicase motifs . Mutations in CSB gene are often found in Cockayne syndrome (CS), an autosomal recessive, segmental progeroid disorder that affects growth, development and maintenance of a wide range of tissues and organs . Specifically patients exhibit growth failure leading to cachectic dwarfism, severe neurological dysfunction, various somatic changes that resemble aging, gait defects and ocular and skeletal abnormalities. Most patients die during childhood. Its penetrance determines to which severity group (Severe, Moderate, Mild and Adult-onset) the patient belongs; clinical manifestations range from complete disability at birth to mildly affected young adults leading a normal life until the onset of the decline . Despite the fact that the two main genes responsible for CS (csb and csa), were cloned more that 20 years ago [5 and 8] and the function(s) of their products, CSA and CSB proteins, have been subject of intense study, there is currently no cure for this syndrome and treatment is only palliative and directed at alleviating some symptoms. Major biological and clinical features of CS are listed in Table 1.