Contribution of p53-dependent and -independent mechanisms to upregulation of p21 in Fanconi anemia
F. Rosselli’s team shows in this article how abnormal p21 expression in Fanconi anemia (FA) contributes to bone marrow failure and genetic instability.
This upregulation depends not only on p53 but also on MITF and its interaction with NPM1.
In FA cells, p21 accumulates on chromatin, binds PCNA, and prolongs S-phase, leading to replication stress.
Depleting p21 restores replication timing and reduces instability.
ROS levels in FA cells promote p21-PCNA association, further impairing DNA replication.
