Coordination of DNA-PK activation and nuclease processing of DNA termini in NHEJ

Katherine S. Pawelczak, Sara M. Bennett, John J. Turchi

Research output: Contribution to journalReview article

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2531-2543
Number of pages13
JournalAntioxidants and Redox Signaling
Volume14
Issue number12
DOIs
StatePublished - Jun 15 2011

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Coordination of DNA-PK activation and nuclease processing of DNA termini in NHEJ'. Together they form a unique fingerprint.

  • Cite this