title: The role of DNA exonucleases in protecting genome stability and their impact on ageing.
abstract: Exonucleases are key enzymes involved in many aspects of cellular metabolism and maintenance and are essential to genome stability, acting to cleave DNA from free ends. Exonucleases can act as proof-readers during DNA polymerisation in DNA replication, to remove unusual DNA structures that arise from problems with DNA replication fork progression, and they can be directly involved in repairing damaged DNA. Several exonucleases have been recently discovered, with potentially critical roles in genome stability and ageing. Here we discuss how both intrinsic and extrinsic exonuclease activities contribute to the fidelity of DNA polymerases in DNA replication. The action of exonucleases in processing DNA intermediates during normal and aberrant DNA replication is then assessed, as is the importance of exonucleases in repair of double-strand breaks and interstrand crosslinks. Finally we examine how exonucleases are involved in maintenance of mitochondrial genome stability. Throughout the review, we assess how nuclease mutation or loss predisposes to a range of clinical diseases and particularly ageing.
authors.affiliation: Department of Biochemistry, University of Oxford, UK. penelope.mason@bioch.ox.ac.uk
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Mason
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Cox
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D000074002:DNA Polymerase gamma; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004720:Endonucleases; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D045585:Flap Endonucleases / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D064251:Multifunctional Enzymes; D010750:Phosphoproteins / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000071657:Werner Syndrome Helicase
chemical_list: D064251:Multifunctional Enzymes; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D004720:Endonucleases; D005090:Exodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; C486104:TREX2 protein, human; C429526:three prime repair exonuclease 1; D004265:DNA Helicases; C509908:DNA2 protein, human; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C085108:APEX1 protein, human; C530688:APEX2 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase