High impact information on POL1

• DNA polymerase I is encoded by the POL1 gene and is essential for DNA replication [1].
• The CDC17 gene product performs an essential stage-specific function during the Saccharomyces cerevisiae cell cycle [2].
• Long telomeres are maintained for many generations when crossed into a CDC17+ background, suggesting that telomere length is largely conserved during replication [2].
• The altered telomere length phenotype of cdc17 mutations is recessive and coreverts and cosegregates with the temperature-sensitive lethal phenotype [2].
• CDC17: an essential gene that prevents telomere elongation in yeast [2].

Biological context of POL1

• Analysis of mRNA levels in cell-cycle-synchronized cultures reveals that the RNR1 mRNA is tightly cell-cycle regulated, fluctuating 15- to 30-fold, and is coordinately regulated with the POL1 mRNA, being expressed in the late G1 and S phases of the cell cycle [3].
• Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1 [4].
• Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis [5].
• We have isolated two high copy, allele-specific suppressors of the temperature sensitivity of mutations in POL1, the gene that encodes the catalytic subunit of DNA polymerase alpha in the yeast Saccharomyces cerevisiae [6].
• The cloned DNA polymerase I gene has been used to map the POL1 locus on the left arm of chromosome XIV, between MET4 and TOP2 [7].

Associations of POL1 with chemical compounds

• MCBs are both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POL1 DNA polymerase genes [8].
• CDC8 was also found to be inducible by DNA damage, but POL1 and URA3 were not inducible by 4-nitroquinoline 1-oxide [9].
• A pol1 temperature-sensitive mutation, encoding a DNA-polymerase-primase complex with altered stability, has a single base-pair substitution that changes the glycine at position 493 to a positively charged arginine [10].
• In each mutant, a single bp substitution, causing the replacement of Gly residues by either Asp (cdc17-1, cdc17-2) or Glu (hpr3) in yeast DNA polymerase I is responsible for the ts phenotype [11].

Physical interactions of POL1

• CDC68 also interacted genetically with POL1 and CTF4 mutations; the maximum permissive temperature of double mutants was lower than for any single mutant [12].
• Pol1p was shown to interact with Cdc13p [13].

Regulatory relationships of POL1

• We propose that Cdc13p's interaction with Est1p promotes TG(1-3) strand lengthening by telomerase and its interaction with Pol1p promotes C(1-3)A strand resynthesis by DNA polymerase alpha [14].

Other interactions of POL1

• Overexpression of Cdc68 in a pol1 mutant strain dramatically decreased cell viability, consistent with the formation or modulation of an essential complex by these proteins in vivo [12].
• Repair synthesis in nuclear extracts of pol1, pol2, and pol3 temperature-sensitive mutants was normal at permissive temperatures [15].
• POL1 (DNA polymerase I) and CDC8 (thymidylate kinase) transcription were unaltered, while histone H2B transcripts actually decreased by half [16].
• Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Pol1 function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing [4].
• The POL1 gene is located on chromosome XIV approximately 2 centimorgans away from met4 [17].

Analytical, diagnostic and therapeutic context of POL1

• In two-hybrid assays, the YJR043c gene product specifically interacted with Pol1, the catalytic subunit of DNA polymerase alpha [18].

References