Inborn Errors Of Metabolism

The activity for AP site excision by XFEN was also stimulated by pol b.Because it was observed only when DNA synthesis was allowed, the stimulation by polbseems to target the flap endonuclease activity.In our experiments, however, the efficiency of AP site excision by XFEN with polbwas comparable to that by XFEN with PCNA and the BE fraction, suggesting that PCNA is not essential for the FEN activity on the flapstructured DNA formed by pol b.Indeed, it has been reported that FEN has a fold higher affinity for the flap structure than the nicked site. Another possibility is that polbmay play the role of PCNA in stimulation of FEN on a flapstructured DNA.However, this possibility was ruled out by our observation that once DNA synthesis displaced several nucleotides of the downstream strand carrying a incised AP site, XFEN was equally active for excision in either the presence or the absence of polb. Thus, the generation of a flap structure is sufficient to explain the stimulation of FEN by pol b.The efficient excision of AP sites by FEN with polballowed the pol bdependent pathway to repair tetrahydrofuran sites that cannot be excised by dRP lyase activity of pol b.These lesions are similar to the tetrahydrofuran sites used in this study for their lack of susceptibility to belimination.Furthermore, it was observed that a pol bknockout cell extract repaired the tetrahydrofuran site as efficiently as a pol bproficient isogenic cell extract. This observation clearly indicates the participation of a DNA polymerase other than pol b, most likely poldor e, in the repair of modified AP sites.Eukaryotes have other structurespecific nucleases and exonucleases in addition to FEN.These enzymes may also serve for excision of altered AP sites.XPG is a protein coded by the gene responsible for the xeroderma pigmentosum G phenotype and is required for nucleotide excision repair.However, the possibility is not ruled out that some other factor that can interact with XPG may be required for excision of AP sites by XPG.The yeast cells lacking the functional RAD or rad gene exhibit various phenotypes, such as moderate sensitivity to UV radiation, hypersensitivity to reasch Norfloxacin methylmethane sulfonate, deficient chromosome segregation, conditional lethality, and accumulation of S phase cells. These phenotypes suggest involvement of FEN homologs in DNA replication, repair, and cell cycle control.Among these phenotypes, the hypersensitivity to the alkylating agent particularly supports our conclusion that FEN is one of the factors employed in base excision repair.Biol. Chem. doi. jbc. Access the most updated version of this article at http:www.jbc.orgcontent When a correction for this article is posted Click here to choose from all of JBCs email alerts This article cites references, of which can be accessed free at http:www.jbc.orgcontent.full.htmlreflist Downloadedfromhttp: www.jbc.orgbyguestonSeptember, Ubiquitination of cellular proteins is a covalent modification that plays several Targetmol’s Naloxone hydrochloride important physiological roles. Proteins become ubiquitinated by the sequential action of three enzymes: a ubiquitinactivating enzyme. This article must therefore be hereby marked advertisement in accordance with U.Such lesions are repaired more rapidly by the NER pathway than are lesions located elsewhere in the genome.

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