Cells have evolved a complex network of biochemical pathways, collectively known as the
DNA damage response (DDR), to prevent detrimental mutations from being passed on to …

Human topoisomerases comprise a family of six enzymes: two type IB (TOP1 and
mitochondrial TOP1 (TOP1MT), two type IIA (TOP2A and TOP2B) and two type IA (TOP3A …

Cancer cells establish replicative immortality by activating a telomere-maintenance
mechanism (TMM), be it telomerase or the alternative lengthening of telomeres (ALT) …

Develo** novel targeted anticancer therapies is a major goal of current research. The use
of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with homologous …

Mutations in BRCA1 or BRCA2 (BRCA) is synthetic lethal with poly (ADP-ribose)
polymerase inhibitors (PARPi). Lethality is thought to derive from DNA double-stranded …

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered
nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the …

The past 25 years of genomics research first revealed which genes are encoded by the
human genome and then a detailed catalogue of human genome variation associated with …

The process of poly (ADP-ribosyl) ation and the major enzyme that catalyses this reaction,
poly (ADP-ribose) polymerase 1 (PARP1), were discovered more than 50 years ago. Since …

Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are the primary
pathways for repairing DNA double-strand breaks (DSBs) during interphase, whereas …

Oxidative and replication stress underlie genomic instability of cancer cells. Amplifying
genomic instability through radiotherapy and chemotherapy has been a powerful but …