| The DNA damage response network has been shown to contribute to tumor suppression by maintaining genomic integrity. Many components of these pathways have been conserved across evolution. Most prominent of which is the novel cell cycle checkpoint/DNA damage repair protein Mus81. Initial studies in yeast identified Mus81 as interacting with Rad54 and Chk2. Recently Mus81 and its partner Eme1 (members of the XPF-ERCC1 subfamily) were shown to possess a junction-resolving activity. Junctions are mostly formed following replication fork regression, or during DNA damage repair. Here we show that transcriptional regulation of Mus81 occurs in a p53-dependent manner. We also show that mice deficient in Mus81 develop to maturity in a C57BL6/J background. Embryonic fibroblasts, T-cells, and B-cells deficient in Mus81 show a marked decrease in proliferative ability supporting Mus81's role in replication fork maintenance. Additionally, homozygous TB cells are sensitive to UV and MMC supporting the role of Mus81 in DNA damage repair. Finally, Mus81 is dispensable for the immune compartment and its overexpression is not enough to elicit a phenotype in Drosophila eyes. |
