TY - JOUR

T1 - Poly(ADP-ribosyl)ation and DNA repair synthesis in the extracts of naked mole rat, mouse, and human cells

AU - Kosova, Anastasiya A.

AU - Kutuzov, Mikhail M.

AU - Evdokimov, Alexei N.

AU - Ilina, Ekaterina S.

AU - Belousova, Ekaterina A.

AU - Romanenko, Svetlana A.

AU - Trifonov, Vladimir A.

AU - Khodyreva, Svetlana N.

AU - Lavrik, Olga I.

N1 - This work was supported by the Russian Science Foundation (project no. 17-74-20075 to MMK). The experiments on affinity labeling of proteins by photoreactive DNAs were supported by the Russian Foundation for Basic Research (project no. 17-00-00097 to SNK).

PY - 2019/5/15

Y1 - 2019/5/15

N2 - DNA repair capacity in cells of naked mole rat (Hgl), a species known for its longevity and resistance to cancer, is still poorly characterized. Here, using the whole-cell extracts (WCEs) of Hgl, mouse and human cells, we studied the interrelation between DNA synthesis on the substrates of base excision repair and the activity of poly(ADP-ribose) polymerases (PARPs) responsible for the transfer of the ADP-ribose moieties onto different targets. The level of PAR synthesis was more than ten-fold higher in human WCE as compared to rodent WCEs, while the efficiency of DNA synthesis was comparable. Under conditions of PAR synthesis, the efficiency of DNA synthesis was only slightly enhanced in all extracts and in mouse WCEs unusual products of the primer elongation were detected. The results obtained with WCEs, recombinant proteins and recently found ability of PARPs to attach the ADP-ribose moieties to DNA allowed us to attribute these products to primer mono(ADPribosyl) ation (MARylation) at the 5'-terminal phosphate by PARP3 during the DNA synthesis. PARP1/PARP2 can then transfer the ADP-ribose moieties onto initial ADP-ribose. Our results suggest that MARylation/PARylation of DNA in the extracts depends on the ratios between PARPs and can be controlled by DNA-binding proteins.

AB - DNA repair capacity in cells of naked mole rat (Hgl), a species known for its longevity and resistance to cancer, is still poorly characterized. Here, using the whole-cell extracts (WCEs) of Hgl, mouse and human cells, we studied the interrelation between DNA synthesis on the substrates of base excision repair and the activity of poly(ADP-ribose) polymerases (PARPs) responsible for the transfer of the ADP-ribose moieties onto different targets. The level of PAR synthesis was more than ten-fold higher in human WCE as compared to rodent WCEs, while the efficiency of DNA synthesis was comparable. Under conditions of PAR synthesis, the efficiency of DNA synthesis was only slightly enhanced in all extracts and in mouse WCEs unusual products of the primer elongation were detected. The results obtained with WCEs, recombinant proteins and recently found ability of PARPs to attach the ADP-ribose moieties to DNA allowed us to attribute these products to primer mono(ADPribosyl) ation (MARylation) at the 5'-terminal phosphate by PARP3 during the DNA synthesis. PARP1/PARP2 can then transfer the ADP-ribose moieties onto initial ADP-ribose. Our results suggest that MARylation/PARylation of DNA in the extracts depends on the ratios between PARPs and can be controlled by DNA-binding proteins.

KW - Base excision repair

KW - DNA polymerase

KW - Heterocephalus glaber

KW - Mus musculus

KW - Poly(ADP-ribose) polymerases

KW - base excision repair

KW - PARP-2

KW - KU

KW - POLYMERASE-BETA

KW - DAMAGE

KW - BASE EXCISION-REPAIR

KW - poly(ADP-ribose) polymerases

KW - ADP-RIBOSYLATION

KW - FLAP ENDONUCLEASE-1

KW - END

KW - HOMOLOGOUS RECOMBINATION

KW - PROTEINS

UR - http://www.scopus.com/inward/record.url?scp=85065805159&partnerID=8YFLogxK

U2 - 10.18632/aging.101959

DO - 10.18632/aging.101959

M3 - Article

C2 - 31085801

AN - SCOPUS:85065805159

VL - 11

SP - 2852

EP - 2873

JO - Aging

JF - Aging

SN - 1945-4589

IS - 9

ER -