Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The methylpurine-DNA glycosylase (MPG) gene coding for human 3-methyladenine (3-meAde)-DNA glycosylase functions in the first step of base excision repair (BER) to remove numerous damaged bases including 3-meGua, ethenoadenine, and hypoxanthine (Hx) in addition to 3-meAde. In this report, we identify the length of the minimal MPG promoter region, demonstrate the involvement of several transcription factors in expression of the MPG gene, and determine the point at which transcription initiates. We also demonstrate that control of MPG expression is linked to MPG activity. To initiate studies on how the MPG functions with the ensemble of BER genes to effect repair, we have investigated the cell cycle control of MPG and other BER genes in normal human cells. Steady-state mRNA levels of MPG, human Nth homologue (NTH), and uracil-DNA glycosylase (UDG), DNA glycosylases, and human AP site-specific endonuclease (APE), an endonuclease incising DNA at abasic sites, are cell cycle dependent. In contrast, expression levels of genes coding for human 8-oxoguanine-DNA glycosylase (OGG1) and TDG DNA glycosylases, and omicron 6-methylguanine-DNA methyltransferase (MGMT) gene, and the RPA4 subunit gene do not vary with cell cycle. These observed cell cycle dependent differences might reflect distinct roles of individual BER proteins in mutation avoidance.
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PMID:Promoter structure and cell cycle dependent expression of the human methylpurine-DNA glycosylase gene. 1098 Apr 9

Replication protein A (RPA) is a heterotrimeric protein complex required for a large number of DNA metabolic processes, including DNA replication and repair. An alternative form of RPA (aRPA) has been described in which the RPA2 subunit (the 32-kDa subunit of RPA and product of the RPA2 gene) of canonical RPA is replaced by a homologous subunit, RPA4. The normal function of aRPA is not known; however, previous studies have shown that it does not support DNA replication in vitro or S-phase progression in vivo. In this work, we show that the RPA4 gene is expressed in normal human tissues and that its expression is decreased in cancerous tissues. To determine whether aRPA plays a role in cellular physiology, we investigated its role in DNA repair. aRPA interacted with both Rad52 and Rad51 and stimulated Rad51 strand exchange. We also showed that, by using a reconstituted reaction, aRPA can support the dual incision/excision reaction of nucleotide excision repair. aRPA is less efficient in nucleotide excision repair than canonical RPA, showing reduced interactions with the repair factor XPA and no stimulation of XPF-ERCC1 endonuclease activity. In contrast, aRPA exhibits higher affinity for damaged DNA than canonical RPA, which may explain its ability to substitute for RPA in the excision step of nucleotide excision repair. Our findings provide the first direct evidence for the function of aRPA in human DNA metabolism and support a model for aRPA functioning in chromosome maintenance functions in nonproliferating cells.
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PMID:An alternative form of replication protein a expressed in normal human tissues supports DNA repair. 1999 5