End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair.
Nonhomologous end joining (NHEJ) is an error-prone DNA double-strand break repair pathway that is active throughout the cell cycle. A substantial fraction of NHEJ repair events show deletions and, less often, insertions in the repair joints, suggesting an end-processing step comprising the removal of mismatched or damaged nucleotides by nucleases and other phosphodiesterases, as well as subsequent strand extension by polymerases. A wide range of nucleases, including Artemis, Metnase, APLF, Mre11, CtIP, APE1, APE2 and WRN, are biochemically competent to carry out such double-strand break end processing, and have been implicated in NHEJ by at least circumstantial evidence. Several additional DNA end-specific phosphodiesterases, including TDP1, TDP2 and aprataxin are available to resolve various non-nucleotide moieties at DSB ends. This review summarizes the biochemical specificities of these enzymes and the evidence for their participation in the NHEJ pathway.
Goodwin Research Laboratory, Massey Cancer Center, Virginia Commonwealth University, VA, 23298-0035, USA.
Vijay
V
Menon
Goodwin Research Laboratory, Massey Cancer Center, Virginia Commonwealth University, VA, 23298-0035, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, VA, 23298-0035, USA. Electronic address: lpovirk@vcu.edu.
Lawrence F
LF
Povirk
D020137:Base Pair Mismatch; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins
C438188:APTX protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; C426344:DCLRE1C protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; C520557:APLF protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA double-strand break repair; End-processing; Nucleases; Phosphodiesterases