Cells with broken DNA MUST NOT go into mitosis.
To avoid this a system of watchdogs exists.
DNA breaks are sensed, and activate kinases :
- ATM (ataxia-telangiectasis mutation)
- ATR (AT rad 3 related).
ATR activates Check Point Kinase 1 (chk1), that inhibits the G2/M checkpoint constituted by Cyclin
dependent kinase 1 (cdk1) and cyclin B.
ATM activates Check Point Kinase 2 (chk2), that
inhibits the G1/S checkpoint constituted by Cyclin
dependent kinase 2 (cdk2) and cyclin E. chk2 also activates p53, then p21, thus inhibiting Cyclin dependent kinase 4 and cyclin D, which leads to inhibition of G2.
These pathways are only part of the picture, and are not completely separate, thanks to "cross-talk".
BRCA1 (absent in 5% of hereditary breast and ovary cancers, decreased in 30% of sporadic) is a key element of the system.
