Neovascularisation is critical in several malignant and inflammatory conditions, as well as in the course of eye disorders. During new vessel formation, endothelial cell functions, such as proliferation and sprouting are very important and are regulated by a variety of growth factors. The DNA damage response machinery as well as factors regulating histone modifications, such as histone deacetylases, regulate cell fate as well as gene expression. Recent evidence has pointed to potential interactions among BRCA1, H2AX and SIRT1 in these intracellular pathways and neovascularisation, which will be reviewed here.