TY - JOUR

T1 - Apurinic/apyrimidinic endonuclease 1 has major impact in prevention of suicidal covalent DNA–protein crosslink with apurinic/apyrimidinic site in cellular extracts

AU - Lebedeva, Natalia A.

AU - Dyrkheeva, Nadezhda S.

AU - Rechkunova, Nadejda I.

AU - Lavrik, Olga I.

N1 - Funding information: Russian Science Foundation,Grant/Award Numbers: 21-64-00017, 22-14-00112; Ministry of Higher Educationand Science

PY - 2024/11

Y1 - 2024/11

N2 - DNA–protein crosslinks (DPC) are common DNA lesions induced by various external and endogenous agents. One of the sources of DPC is the apurinic/apyrimidinic site (AP site) and proteins interacting with it. Some proteins possessing AP lyase activity form covalent complexes with AP site-containing DNA without borohydride reduction (suicidal crosslinks). We have shown earlier that tyrosyl-DNA phosphodiesterase 1 (TDP1) but not AP endonuclease 1 (APE1) is able to remove intact OGG1 from protein–DNA adducts, whereas APE1 is able to prevent the formation of DPC by hydrolyzing the AP site. Here we demonstrate that TDP1 can remove intact PARP2 but not XRCC1 from covalent enzyme–DNA adducts with AP-DNA formed in the absence of APE1. We also analyzed an impact of APE1 and TDP1 on the efficiency of DPC formation in APE1−/− or TDP1−/− cell extracts. Our data revealed that APE1 depletion leads to increased levels of PARP1–DNA crosslinks, whereas TDP1 deficiency has little effect on DPC formation.

AB - DNA–protein crosslinks (DPC) are common DNA lesions induced by various external and endogenous agents. One of the sources of DPC is the apurinic/apyrimidinic site (AP site) and proteins interacting with it. Some proteins possessing AP lyase activity form covalent complexes with AP site-containing DNA without borohydride reduction (suicidal crosslinks). We have shown earlier that tyrosyl-DNA phosphodiesterase 1 (TDP1) but not AP endonuclease 1 (APE1) is able to remove intact OGG1 from protein–DNA adducts, whereas APE1 is able to prevent the formation of DPC by hydrolyzing the AP site. Here we demonstrate that TDP1 can remove intact PARP2 but not XRCC1 from covalent enzyme–DNA adducts with AP-DNA formed in the absence of APE1. We also analyzed an impact of APE1 and TDP1 on the efficiency of DPC formation in APE1−/− or TDP1−/− cell extracts. Our data revealed that APE1 depletion leads to increased levels of PARP1–DNA crosslinks, whereas TDP1 deficiency has little effect on DPC formation.

KW - AP endonuclease 1

KW - DNA–protein crosslinks

KW - apurinic/apyrimidinic site

KW - poly(ADP-ribose) polymerases

KW - tyrosyl-DNA phosphodiesterase 1

KW - DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism

KW - Phosphoric Diester Hydrolases/metabolism

KW - Humans

KW - DNA/metabolism

KW - Animals

KW - X-ray Repair Cross Complementing Protein 1/metabolism

KW - Cell Extracts/chemistry

KW - DNA Repair

KW - Mice

KW - DNA Adducts/metabolism

KW - DNA-Binding Proteins/genetics

KW - DNA Damage

KW - Poly(ADP-ribose) Polymerases/metabolism

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85197510442&origin=inward&txGid=00536e9eb862eb737e65d7ec0ddc8c29

UR - https://www.mendeley.com/catalogue/4e620e46-0797-38cc-a164-7cd1d01ff522/

U2 - 10.1002/iub.2890

DO - 10.1002/iub.2890

M3 - Article

C2 - 38963041

VL - 76

SP - 987

EP - 996

JO - IUBMB Life

JF - IUBMB Life

SN - 1521-6543

IS - 11

ER -