8ka5

From Proteopedia

Arabidopsis AP endonuclease ARP complex with 20bp THF-containing DNA

Structural highlights

8ka5 is a 4 chain structure with sequence from Arabidopsis thaliana and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARP_ARATH Repairs oxidative DNA damages, seems also to act as a redox factor (PubMed:7512729). Is multifunctional and may be involved both in DNA repair and in the regulation of transcription (PubMed:7512729). Exhibits apurinic/apyrimidinic (AP) endonuclease activity (PubMed:21781197, PubMed:25228464, PubMed:25569774). Catalyzes the conversion of 3'-phosphor-alpha,beta-unsaturated aldehyde (3'-PUA) to 3'-OH (PubMed:25228464). May be involved in base excision repair in chloroplasts (PubMed:19372224). According to a report, has a significant in vitro 3'-phosphatase activity (PubMed:25228464). According to another report, has no in vitro 3'-phosphatase activity (PubMed:25569774). Has a strong non-specific affinity to DNA (PubMed:25228464).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease AtARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in AtARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of AtARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.

Structural insights into the catalytic mechanism of the AP endonuclease AtARP.,Guo W, Wu W, Wen Y, Gao Y, Zhuang S, Meng C, Chen H, Zhao Z, Hu K, Wu B Structure. 2024 Mar 8:S0969-2126(24)00053-4. doi: 10.1016/j.str.2024.02.014. PMID:38503293^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gutman BL, Niyogi KK. Evidence for base excision repair of oxidative DNA damage in chloroplasts of Arabidopsis thaliana. J Biol Chem. 2009 Jun 19;284(25):17006-17012. PMID:19372224 doi:10.1074/jbc.M109.008342
↑ Córdoba-Cañero D, Roldán-Arjona T, Ariza RR. Arabidopsis ARP endonuclease functions in a branched base excision DNA repair pathway completed by LIG1. Plant J. 2011 Nov;68(4):693-702. PMID:21781197 doi:10.1111/j.1365-313X.2011.04720.x
↑ Lee J, Jang H, Shin H, Choi WL, Mok YG, Huh JH. AP endonucleases process 5-methylcytosine excision intermediates during active DNA demethylation in Arabidopsis. Nucleic Acids Res. 2014 Oct;42(18):11408-18. doi: 10.1093/nar/gku834. Epub 2014 , Sep 16. PMID:25228464 doi:http://dx.doi.org/10.1093/nar/gku834
↑ Li Y, Córdoba-Cañero D, Qian W, Zhu X, Tang K, Zhang H, Ariza RR, Roldán-Arjona T, Zhu JK. An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis [corrected]. PLoS Genet. 2015 Jan 8;11(1):e1004905. PMID:25569774 doi:10.1371/journal.pgen.1004905
↑ Babiychuk E, Kushnir S, Van Montagu M, Inzé D. The Arabidopsis thaliana apurinic endonuclease Arp reduces human transcription factors Fos and Jun. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3299-303. PMID:7512729 doi:10.1073/pnas.91.8.3299
↑ Murphy TM, Belmonte M, Shu S, Britt AB, Hatteroth J. Requirement for abasic endonuclease gene homologues in Arabidopsis seed development. PLoS One. 2009;4(1):e4297. PMID:19172180 doi:10.1371/journal.pone.0004297
↑ Guo W, Wu W, Wen Y, Gao Y, Zhuang S, Meng C, Chen H, Zhao Z, Hu K, Wu B. Structural insights into the catalytic mechanism of the AP endonuclease AtARP. Structure. 2024 Mar 8:S0969-2126(24)00053-4. PMID:38503293 doi:10.1016/j.str.2024.02.014