CHEK1
Description
The CHEK1 (checkpoint kinase 1) is a protein-coding gene located on chromosome 11.
Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle.
== Discovery == In 1993, Beach and associates initially identified Chk1 as a serine/threonine kinase which regulates the G2/M phase transition in fission yeast. Constitutive expression of Chk1 in fission yeast was shown to induce cell cycle arrest. The same gene called Rad27 was identified in budding yeast by Carr and associates. In 1997, homologs were identified in more complex organisms including the fruit fly, human and mouse. Through these findings, it is apparent Chk1 is highly conserved from yeast to humans.
== Structure == Human Chk1 is located on chromosome 11 on the cytogenic band 11q22-23. Chk1 has a N-terminal kinase domain, a linker region, a regulatory SQ/TQ domain and a C-terminal domain.
CHEK1, also known as CHK1 checkpoint homolog, Cell cycle checkpoint kinase, Checkpoint kinase-1, is a serine/threonine-protein kinase that is essential for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to DNA damage or unreplicated DNA. It also plays a role in negatively regulating cell cycle progression during unperturbed cell cycles. CHEK1 achieves this regulation through multiple mechanisms that collectively contribute to maintaining the integrity of the genome. CHEK1 recognizes the substrate consensus sequence [R-X-X- S/T]. It binds to and phosphorylates CDC25A, CDC25B, and CDC25C, leading to the inhibition of CDC25A and CDC25C by 14-3-3 proteins. Phosphorylation of CDC25A promotes its proteolysis. CHEK1 also phosphorylates NEK6, RAD51, TP53, FANCE, TLK1, histone H3.1, RB1, SPRTN, PABIR1/FAM122A, and WEE1. CHEK1 interacts with RAD51, CLSPN, BRCA1, FBXO6, PPM1D, TIMELESS, FEM1B, TLK1, XPO1, YWHAZ, CDK5RAP3, and its own isoforms 1 and 2.
CHEK1 is also known as CHK1, OZEMA21.
