Back-Up Base Excision DNA Repair in Human Cells Deficient in the Major AP Endonuclease, APE1 | Sciact - CRIS-system of Boreskov Institute of Catalysis

Back-Up Base Excision DNA Repair in Human Cells Deficient in the Major AP Endonuclease, APE1 Full article

Journal

International Journal of Molecular Sciences
ISSN: 1422-0067 , E-ISSN: 1661-6596

Output data

Year: 2024, Volume: 25, Number: 1, Article number : 64, Pages count : 16 DOI: 10.3390/ijms25010064

Tags

DNA repair; abasic sites; uracil; AP endonucleases; DNA glycosylases; APE1; APE2; NTHL1

Authors

Kim Daria V. ^1,2 , Diatlova Evgeniia A. ¹ , Zharkov Timofey D. ¹ , Melentyev Vasily S. ^1,2 , Yudkina Anna V. ^1,2 , Endutkin Anton V. ¹ , Zharkov Dmitry O. ^1,2

Affiliations

1	Siberian Branch of the Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia
2	Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St., 630090 Novosibirsk, Russia

Apurinic/apyrimidinic (AP) sites are abundant DNA lesions generated both by spontaneous base loss and as intermediates of base excision DNA repair. In human cells, they are normally repaired by an essential AP endonuclease, APE1, encoded by the APEX1 gene. Other enzymes can cleave AP sites by either hydrolysis or β-elimination in vitro, but it is not clear whether they provide the second line of defense in living cells. Here, we studied AP site repairs in APEX1 knockout derivatives of HEK293FT cells using a reporter system based on transcriptional mutagenesis in the enhanced green fluorescent protein gene. Despite an apparent lack of AP site-processing activity in vitro, the cells efficiently repaired the tetrahydrofuran AP site analog resistant to β-elimination. This ability persisted even when the second AP endonuclease homolog, APE2, was also knocked out. Moreover, APEX1 null cells were able to repair uracil, a DNA lesion that is removed via the formation of an AP site. If AP site hydrolysis was chemically blocked, the uracil repair required the presence of NTHL1, an enzyme that catalyzes β-elimination. Our results suggest that human cells possess at least two back-up AP site repair pathways, one of which is NTHL1-dependent.

Kim D.V. , Diatlova E.A. , Zharkov T.D. , Melentyev V.S. , Yudkina A.V. , Endutkin A.V. , Zharkov D.O.
Back-Up Base Excision DNA Repair in Human Cells Deficient in the Major AP Endonuclease, APE1
International Journal of Molecular Sciences. 2024. V.25. N1. 64 :1-16. DOI: 10.3390/ijms25010064 WOS Scopus ANCAN PMID OpenAlex

Submitted:	Nov 15, 2023
Accepted:	Dec 18, 2023
Published online:	Dec 20, 2023
Published print:	Jan 1, 2024

Web of science:	WOS:001140627800001
Scopus:	2-s2.0-85182094784
Chemical Abstracts:	2024:136866
Chemical Abstracts (print):	185:276553
PMID:	38203235
OpenAlex:	W4390007442

DB	Citing
OpenAlex	4
Web of science	3
Scopus	4