Repair of ionizing radiation-induced DNA double strand breaks by non-homologous end-joining

By Brandi L. Mahaney, K. Meek, S. Lees-Miller. Biochemical Journal, 2009

731 citations recorded by the source corpus.

DNA double strand breaks (DSBs) are considered the most cytotoxic type of DNA lesion. They can be introduced by external sources such as ionizing radiation (IR), by chemotherapeutic drugs such as topoisomerase poisons and by normal biological processes such as V(D)J recombination. If left unrepaired, DSBs can cause cell death. If misrepaired, DSBs may lead to chromosomal translocations and genomic instability. One of the major pathways for the repair of IR-induced DSBs in mammalian cells is non-homologous end-joining (NHEJ). The main proteins required for NHEJ in mammalian cells are the Ku heterodimer, the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), Artemis, XRCC4, DNA ligase IV and XLF (XRCC4-like factor, also called Cernunnos). Additional proteins including DNA polymerases μ and λ, polynucleotide kinase (PNK) and the Werner’s Syndrome helicase (WRN) may also play a role. Here, we will review our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ.

Subfields: Cancer Research, Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/9c06d4bd1781bd1ac21be91b8a7f6345fef5e18f

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M. Lieber

Citations in the corpus

How shelterin solves the telomere end-protection problem. (2010, background): “For primary references and more extensive details on these pathways, the reader is referred to excellent recent reviews on these subjects (Hefferin and Tomkinson 2005; Harper and Elledge 2007; Cimprich and Cortez 2008; Jackson and Bartek 2009; Mahaney et al. 2009; Mimitou and Symington 2009; Lieber ”
The DNA Damage Response: Making it safe to play with knives (2010, background): “(B) DNA lesions induced by UV light or replication stress (denoted by red rectang ssDNA regions, which recruit the ATR/ATRIP and the RAD17/RFC2-5 complexes kinase activity by the 9-1-1-associated protein TOPBP1 result in the activation of fications of the DDR factors depicted here are represented by”
The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End Joining Pathway (2010, background): “Activated DNA-PKcs stimulates the ligase activity of XRCC4:DNA ligase IV (90, 95, 96).”
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining (2010, neutral): “as well as other factors, including the nuclease Artemis and the Ligase IV–XRCC4 complex, which are required for NHEJ to ensu”