DNA damage signalling, repair and cancer
DNA double-strand breaks (DSBs) represent the most lethal form of DNA damage. Indeed, a single, unrepaired DSB is thought to be sufficient to cause cell death. Mainly for this reason, agents that cause DSBs are at the root of our anti-cancer therapeutics. DSBs can result from exposure to exogenous genotoxins, such as ionizing radiation (IR) and chemotherapeutic drugs, or as a consequence of intrinsic cellular processes such as DNA replication and metabolic processes that generate DNA-damaging free radicals. In addition to being essential for cell survival, DSBs are a potent cause of genomic rearrangements. If left unrepaired, DSBs can result in the loss of genetic material and DSBs are an obligate intermediate of numerous types of gross genetic aberrations such as chromosome translocations. Given the critical importance of DSBs in cancer etiology and therapy, the study of the cellular response to DSBs is of utmost importance to cancer biology.
In vertebrates, there are two principal DSB repair pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). HR acts primarily after DNA replication where it accurately repairs the DSB using the undamaged sister-chromatid as a DNA template. On the other hand, NHEJ is active throughout the cell cycle, predominating during G0 and G1, is error-prone and uses little or no sequence homology to repair DSBs. NHEJ is the major pathway involved in the repair of DSBs induced by DNA damaging agents, such as IR or radio-mimetic drugs. By virtue of its importance in promoting repair of DSBs caused by therapeutic IR and anti-cancer drugs, the study of NHEJ is germane for the development novel anti-cancer therapies.
Our laboratory is focused on studies examining the complex regulation of the DNA damage response and how its deregulation relates to carcinogenesis. Some of our specific research interests include the identification and characterization of novel DNA damage signalling pathways and repair factors involved in the cellular response to IR-induced DNA damage. We are also interested in the detailed examination of these pathways and how they may be perturbed in the context of human breast cancer.
DNA double-strand breaks (DSBs) represent the most lethal form of DNA damage. Indeed, a single, unrepaired DSB is thought to be sufficient to cause cell death. Mainly for this reason, agents that cause DSBs are at the root of our anti-cancer therapeutics. DSBs can result from exposure to exogenous genotoxins, such as ionizing radiation (IR) and chemotherapeutic drugs, or as a consequence of intrinsic cellular processes such as DNA replication and metabolic processes that generate DNA-damaging free radicals. In addition to being essential for cell survival, DSBs are a potent cause of genomic rearrangements. If left unrepaired, DSBs can result in the loss of genetic material and DSBs are an obligate intermediate of numerous types of gross genetic aberrations such as chromosome translocations. Given the critical importance of DSBs in cancer etiology and therapy, the study of the cellular response to DSBs is of utmost importance to cancer biology.
In vertebrates, there are two principal DSB repair pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). HR acts primarily after DNA replication where it accurately repairs the DSB using the undamaged sister-chromatid as a DNA template. On the other hand, NHEJ is active throughout the cell cycle, predominating during G0 and G1, is error-prone and uses little or no sequence homology to repair DSBs. NHEJ is the major pathway involved in the repair of DSBs induced by DNA damaging agents, such as IR or radio-mimetic drugs. By virtue of its importance in promoting repair of DSBs caused by therapeutic IR and anti-cancer drugs, the study of NHEJ is germane for the development novel anti-cancer therapies.
Our laboratory is focused on studies examining the complex regulation of the DNA damage response and how its deregulation relates to carcinogenesis. Some of our specific research interests include the identification and characterization of novel DNA damage signalling pathways and repair factors involved in the cellular response to IR-induced DNA damage. We are also interested in the detailed examination of these pathways and how they may be perturbed in the context of human breast cancer.