The optimal strategy balancing risk and speed predicts DNA damage checkpoint override times

ABSTRACT: Checkpoints arrest biological processes allowing time for error correction. The phenomenon of checkpoint override (also known as checkpoint adaptation, slippage, or leakage), during cellular self-replication is biologically critical but currently lacks a quantitative, functional, or system-level understanding. To uncover fundamental laws governing error-correction systems, we derived a general theory of optimal checkpoint strategies, balancing the trade-off between risk and self-replication speed. Mathematically, the problem maps onto the optimization of an absorbing boundary for a random walk. We applied the theory to the DNA damage checkpoint (DDC) in budding yeast, an intensively researched model checkpoint. Using novel reporters for double-strand DNA breaks (DSBs), we first quantified

SUBMITTER: Sadeghi A 

PROVIDER: S-EPMC7613727 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature