TP53, encoding a stress-activated transcription factor, is commonly mutated in human cancers. Most of these mutations are missense mutations which, in the presence of WT-p53 (p53mut/+), can cause loss of function (LOF), dominant-negative (DN) and/or gain of function (GOF) activities. However, mutant p53 is more commonly studied following loss-of-heterozygosity (p53mut/-) which is thought to promote tumorigenesis. The functionality of mutant-p53 in early tumorigenesis (p53mut/+) has been underexplored but it may uncover how the mutation primes a cell for aberrant activities. By modelling the heterozygous expression of p53R175H in unstressed, acute- and chronic-stress conditions (DNA damage induced senescence, DDIS), I have identified potential DN and GOF activities and the underlying molecular mechanism using the latest -omics and chromatin binding assays. Despite the DN activity being strong and p53R175H-dose-dependent in acute stress, the cells show a stress-dependent cell fitness response, with the chronic stress state making the heterozygous p53R175H less fit than WT-cells.