Work

Coordination of DNA–PK Activation and Nuclease Processing of DNA Termini in NHEJ

Year: 2010

Type: review

Abstract: DNA double-strand breaks (DSB), particularly those induced by ionizing radiation (IR), are complex lesions that can be cytotoxic if not properly repaired. IR-induced DSB often have DNA termini modifications, including thymine glycols, ring fragmentation, 3'-phosphoglycolates, 5'-hydroxyl groups, and abasic sites. Nonhomologous end joining (NHEJ) is a major pathway responsible for the repair of these complex breaks. Proteins involved in NHEJ include the Ku 70/80 heterodimer, DNA-PKcs, processing proteins including Artemis and DNA polymerases μ and λ, XRCC4, DNA ligase IV, and XLF. We will discuss the role of the physical and functional interactions of DNA-PK as a result of activation, with an emphasis on DNA structure, chemistry, and sequence. With the diversity of IR induced DSB, it is becoming increasingly clear that multiple DNA processing enzymes are likely necessary for effective repair of a break. We will explore the roles of several important processing enzymes, with a focus on the nuclease Artemis and its role in processing diverse DSB. The effect of DNA termini on both DNA-PK and Artemis activity will be analyzed from a structural and biochemical view.

Source: Antioxidants and Redox Signaling

DOI: 10.1089/ars.2010.3368

Authors: Katherine S Pawelczak, Sara M Bennett, John J Turchi

Institutions: Indiana University School of Medicine, Indiana University Indianapolis

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute

Awards: Recognition and Repair of Cisplatin-DNA Damage, Development of methodologies for the analysis of DNA repair capacity to predict t