title: Effect of the multifunctional proteins RPA, YB-1, and XPC repair factor on AP site cleavage by DNA glycosylase NEIL1.
abstract: DNA glycosylases are key enzymes in the first step of base excision DNA repair, recognizing DNA damage and catalyzing the release of damaged nucleobases. Bifunctional DNA glycosylases also possess associated apurinic/apyrimidinic (AP) lyase activity that nick the damaged DNA strand at an abasic (or AP) site, formed either spontaneously or at the first step of repair. NEIL1 is a bifunctional DNA glycosylase capable of processing lesions, including AP sites, not only in double-stranded but also in single-stranded DNA. Here, we show that proteins participating in DNA damage response, YB-1 and RPA, affect AP site cleavage by NEIL1. Stimulation of the AP lyase activity of NEIL1 was observed when an AP site was located in a 60 nt-long double-stranded DNA. Both RPA and YB-1 inhibited AP site cleavage by NEIL1 when the AP site was located in single-stranded DNA. Taking into account a direct interaction of YB-1 with the AP site, located in single-stranded DNA, and the high affinity of both YB-1 and RPA for single-stranded DNA, this behavior is presumably a consequence of a competition with NEIL1 for the DNA substrate. Xeroderma pigmentosum complementation group C protein (XPC), a key protein of another DNA repair pathway, was shown to interact directly with AP sites but had no effect on AP site cleavage by NEIL1.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Prospect Lavrentieva 8, Novosibirsk, 630090, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pestryakov
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Zharkov
authors.forename: Inga
authors.initials: I
authors.lastname: Grin
authors.forename: Elizaveta E
authors.initials: EE
authors.lastname: Fomina
authors.forename: Ekaterina R
authors.initials: ER
authors.lastname: Kim
authors.forename: Loïc
authors.initials: L
authors.lastname: Hamon
authors.forename: Irina A
authors.initials: IA
authors.lastname: Eliseeva
authors.forename: Irina O
authors.initials: IO
authors.lastname: Petruseva
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Curmi
authors.forename: Lev P
authors.initials: LP
authors.lastname: Ovchinnikov
authors.forename: Olga I
authors.initials: OI
authors.lastname: Lavrik
mesh_terms: D000818:Animals; D001080:Apurinic Acid / Q000737:chemistry; D001894:Borohydrides / Q000737:chemistry; D053837:DNA Cleavage; D045647:DNA Glycosylases / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D051379:Mice; D011119:Polynucleotides / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D051716:Replication Protein A / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D001080:Apurinic Acid; D001894:Borohydrides; D045647:DNA Glycosylases; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D011119:Polynucleotides; D051716:Replication Protein A; D012545:Schiff Bases; D014157:Transcription Factors; C501002:Xpc protein, mouse; C541744:Ybx1 protein, mouse; C001790:apyrimidinic acid; C025364:sodium borohydride; C481347:Neil1 protein, mouse