Disease relevance of PHR1

• The PHR1 protein complements a photolyase-deficient mutant of Escherichia coli and thus confers photoreactivation activity [1].
• Recent biochemical studies demonstrate that the Cryptochrome-Drosophila, Arabidopsis, Synechocystis, Human (Cry-DASH) subfamily of cryptochromes have photolyase activity exclusively for single-stranded cyclobutane pyrimidine dimer (CPD)-containing DNA substrate [Selby C, Sancar A (2006) Proc Natl Acad Sci USA 103:17696-17700] [2].

High impact information on PHR1

• Increases in recombination are accompanied by a strong induction of photolyase and Rad51 gene expression [3].
• Despite the sequence homology to microbial DNA photolyases, CRY1 was found to have no detectable photolyase activity [4].
• One of the mutants, phr1 (phosphate starvation response 1), displayed reduced response of AtIPS1::GUS to Pi starvation, and also had a broad range of Pi starvation responses impaired, including the responsiveness of various other Pi starvation-induced genes and metabolic responses, such as the increase in anthocyanin accumulation [5].
• We conclude that PHR1 represents a genuine plant photolyase gene and that the plant genes with homology to type I photolyases (the cryptochrome family of blue light photoreceptors) do not contribute to photoreactivation repair, at least in the case of Arabidopsis [1].
• Instead, the PHR1 gene encodes an amino acid sequence with significant homology to the recently characterized type II photolyases identified in a number of prokaryotic and animal systems [1].

Chemical compound and disease context of PHR1

• Here we demonstrate that substitution of two conserved tryptophans that are constituents of the flavin-reducing electron transfer chain in Escherichia coli photolyase impairs light-induced electron transfer in the Arabidopsis cryptochrome-1 photoreceptor in vitro [6].

Biological context of PHR1

• This recessive mutation segregates as a single gene located near the top of chromosome 1, and is a structural gene mutation in the type II CPD photolyase PHR1 [7].
• We demonstrate that the CPD photolyase mutation is genetically linked to a DNA sequence encoding a type II (metazoan) CPD photolyase [8].
• PHR1 binding sites were more frequent in promoters of P-regulated genes as compared to the entire Arabidopsis genome, and E2F and PHR1 binding sites were more frequent in interaction clusters 1 and 3, respectively [9].
• In order to know the molecular mechanism by which PHR1 gene expression is induced by light, we have determined the genomic structure and the 5'-flanking sequence of the Arabidopsis PHR1 gene [10].
• The PHR1 gene spans approximately 2.5 kb of genomic DNA and consists of 9 exons [10].

Associations of PHR1 with chemical compounds

• UVR2 and UVR3 products were previously identified as photolyases that remove UV-induced pyrimidine dimers in the presence of visible light [11].
• It has recently been shown that Arabidopsis cryptochrome-1 retains photolyase-like photoreduction of its flavin cofactor FAD by intraprotein electron transfer from tryptophan and tyrosine residues [6].
• Like class I photolyase, the Arabidopsis enzyme contains FAD but a second chromophore was not detectable [12].
• Photolyase/blue-light photoreceptor family of proteins includes cyclobutane pyrimidine dimer photolyase, (6-4) photolyase and blue-light photoreceptors that were recently discovered in Arabidopsis thaliana, Sinapis alba and Chlamydomonas reinhardtii [13].
• Reduced FADH and a reduced pterin were identified as cofactors of the native Arabidopsis CPD photolyase protein [14].

Other interactions of PHR1

• PHR1 is a single-copy gene and is not expressed in dark-grown etiolated seedlings: the message is light inducible, which is similar to the expression profile for photoreactivation activity in plants [1].
• We describe the isolation and characterization of two new classes of mutants of Arabidopsis, termed uvr2 and uvr3, that are defective in the photoreactivation of CPDs and 6-4 products, respectively [8].
• Cryptochromes 1 and 2 are photolyase-like receptors that regulate hypocotyl growth and flowering time; phototropin mediates phototropism in response to blue light [15].

Analytical, diagnostic and therapeutic context of PHR1

• Characteristic structure and environment in FAD cofactor of (6-4) photolyase along function revealed by resonance Raman spectroscopy [16].
• Molecular cloning of Arabidopsis photolyase gene (PHR1) and characterization of its promoter region [10].

References