TY - JOUR

T1 - Repair of abasic sites in DNA.

AU - Dianov, Grigory L.

AU - Sleeth, Kate M.

AU - Dianova, Irina I.

AU - Allinson, Sarah L.

PY - 2003/10/29

Y1 - 2003/10/29

N2 - Repair of both normal and reduced AP sites is activated by AP endonuclease, which recognizes and cleaves a phosphodiester bond 5′ to the AP site. For a short period of time an incised AP site is occupied by poly(ADP-ribose) polymerase and then DNA polymerase β adds one nucleotide into the repair gap and simultaneously removes the 5′-sugar phosphate. Finally, the DNA ligase III/XRCC1 complex accomplishes repair by sealing disrupted DNA ends. However, long-patch BER pathway, which is involved in the removal of reduced abasic sites, requires further DNA synthesis resulting in strand displacement and the generation of a damage-containing flap that is later removed by the flap endonuclease. Strand-displacement DNA synthesis is accomplished by DNA polymerase δ/ and DNA ligase I restores DNA integrity. DNA synthesis by DNA polymerase δ/ is dependent on proliferating cell nuclear antigen, which also stimulates the DNA ligase I and flap endonuclease. These repair events are supported by multiple protein–protein interactions.

AB - Repair of both normal and reduced AP sites is activated by AP endonuclease, which recognizes and cleaves a phosphodiester bond 5′ to the AP site. For a short period of time an incised AP site is occupied by poly(ADP-ribose) polymerase and then DNA polymerase β adds one nucleotide into the repair gap and simultaneously removes the 5′-sugar phosphate. Finally, the DNA ligase III/XRCC1 complex accomplishes repair by sealing disrupted DNA ends. However, long-patch BER pathway, which is involved in the removal of reduced abasic sites, requires further DNA synthesis resulting in strand displacement and the generation of a damage-containing flap that is later removed by the flap endonuclease. Strand-displacement DNA synthesis is accomplished by DNA polymerase δ/ and DNA ligase I restores DNA integrity. DNA synthesis by DNA polymerase δ/ is dependent on proliferating cell nuclear antigen, which also stimulates the DNA ligase I and flap endonuclease. These repair events are supported by multiple protein–protein interactions.

KW - Abasic sites

KW - DNA

KW - Alkylating agents

U2 - 10.1016/j.mrfmmm.2003.09.003

DO - 10.1016/j.mrfmmm.2003.09.003

M3 - Journal article

VL - 531

SP - 157

EP - 163

JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

SN - 0027-5107

IS - 1-2

ER -