Mus81-flox Mouse

Mus81, an important structure-specific endonuclease, is involved in DNA repair processes. It functions by forming complexes with regulatory subunits like EME1 and EME2, playing distinct roles in different cell cycle phases such as G2/M and S phases [4]. It participates in pathways related to resolving replication and recombination intermediates, and is thought to be crucial for ensuring proper chromosome segregation during cell division [2].

Research has shown that MUS81 is dispensable for embryonic development and cell viability in mammals [1]. In rice, MUS81 contributes little to crossover designation but is required for the resolution of atypical recombination intermediates [3]. In human cancers, discrepant gene mutations can completely alter its role. For example, in gastric cancer, MUS81 knockdown enhanced the anticancer effect of the PARP inhibitor talazoparib by impairing the ATR/CHK1 cell cycle signaling pathway [6]. In castration-resistant prostate cancer, MUS81 silencing inhibited cell proliferation and promoted sensitivity to Olaparib [7]. Also, in microsatellite-unstable cancers, in the absence of WRN helicase, expanded TA-dinucleotide repeats are cleaved by MUS81 nuclease, leading to chromosome shattering [5].

In conclusion, Mus81 plays a vital role in DNA repair, especially in resolving specific DNA structures during replication and recombination. Gene knockout and related functional studies in various models, including mouse models in cancer research, have revealed its significance in different disease conditions. Understanding Mus81's functions provides potential therapeutic strategies, especially in cancer treatment.