DNA damage recognition and repair pathway coordination revealed by the structural biochemistry of DNA repair enzymes.
Cells have evolved distinct mechanisms for both preventing and removing mutagenic and lethal DNA damage. Structural and biochemical characterization of key enzymes that function in DNA repair pathways are illuminating the biological and chemical mechanisms that govern initial lesion detection, recognition, and excision repair of damaged DNA. These results are beginning to reveal a higher level of DNA repair coordination that ensures the faithful repair of damaged DNA. Enzyme-induced DNA distortions allow for the specific recognition of distinct extrahelical lesions, as well as tight binding to cleaved products, which has implications for the ordered transfer of unstable DNA repair intermediates between enzymes during base excision repair.
Hosfield
D J
DJ
Department of Molecular Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Daniels
D S
DS
Mol
C D
CD
Putnam
C D
CD
Parikh
S S
SS
Tainer
J A
JA
D000478:Alkylation; D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000737:chemistry / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004249:DNA Damage; D045647:DNA Glycosylases; D011088:DNA Ligases / Q000737:chemistry / Q000502:physiology*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000502:physiology; D045585:Flap Endonucleases; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D011755:Pyrophosphatases / Q000737:chemistry / Q000502:physiology; D051981:Uracil-DNA Glycosidase
D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D043223:Deoxyribonuclease IV (Phage T4-Induced); C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C076131:DNA-3-methyladenine glycosidase II; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases