ChkB

ChkB, also known as Checkpoint kinase 2, is a protein that plays a crucial role in the DNA damage response pathway in cells. It is encoded by the CHEK2 gene in humans. ChkB is a serine/threonine-specific protein kinase that becomes activated in response to DNA damage or replication stress. Its primary function is to halt cell cycle progression, allowing time for DNA repair mechanisms to rectify the damage and maintain genomic stability.

Upon activation, ChkB phosphorylates and inactivates Cdc25 phosphatases, which are responsible for removing inhibitory phosphates from cyclin-dependent kinases (Cdks). By inhibiting Cdc25, ChkB prevents the activation of Cdks, leading to cell cycle arrest at various checkpoints, notably the G1/S and G2/M transitions. This arrest provides cells with an opportunity to repair damaged DNA before proceeding to the next phase of the cell cycle.

Mutations in the CHEK2 gene have been linked to an increased risk of various cancers, including breast, prostate, and thyroid cancer. These mutations can impair the function of ChkB, leading to a reduced ability to respond to DNA damage and an increased likelihood of genomic instability. As a result, ChkB has been the subject of extensive research as a potential target for cancer therapy.

In summary, ChkB is a critical component of the cellular response to DNA damage, ensuring genomic integrity by regulating cell cycle progression. Its role in maintaining genomic stability and its association with cancer risk highlight the importance of understanding its function and regulation.