Disease relevance of POLD1

• Effect of exogenous MSH6 and POLD1 expression on the mutation rate of the HPRT locus in a human colon cancer cell line with mutator phenotype, DLD-1 [1].
• Characterization of the human DNA polymerase delta catalytic subunit expressed by a recombinant baculovirus [2].

High impact information on POLD1

• We identified 11 hotspot loci of LOH/AI in the BRCA1/2 stroma, encompassing genes such as POLD1, which functions in DNA replication, and SDHB [3].
• When ectopic wild-type p53 expression was induced to a physiologically relevant level in "tet-off" cultured cells in which p53 expression was tightly regulated by tetracycline, it was found that POLD1 steady-state mRNA was repressed by about 65% [4].
• Northern blotting showed that a significantly decreased steady-state level of POLD1 mRNA was associated with increased wild-type p53 expression in cells treated with methyl methanesulfonate [4].
• The promoter of the human POLD1 gene encoding the catalytic subunit of DNA polymerase delta is G/C-rich and does not contain a TATA box [5].
• Multiple elements in this region including two 11-bp direct repeats located between nucleotide positions -92 and -22, play an important role in POLD1 promoter activity [5].

Biological context of POLD1

• Sequencing analyses on the genomic DNA and cDNA of the POLD1 gene revealed that DLD-1 cells are a mixture of two distinct sublines with regard to POLD1 genotypes [1].
• Since DLD-1 carries frameshift mutations in both alleles of the MSH6 gene and missense mutations in the POLD1 gene, either or both of these mutations were suggested to be involved in this mutator phenotype [1].
• The results indicated that the breakpoint is located between POLD1 and TRPT at the boundary between chromosome bands 19q13.3 and 19q13.4 [6].
• The human POLD1 gene. Identification of an upstream activator sequence, activation by Sp1 and Sp3, and cell cycle regulation [5].
• We have used these cell lines and four additional primary tumors with 19q13 abnormalities for fluorescence in situ hybridization (FISH) mapping studies with ten cosmid clones located between the molecular markers POLD1 and TNNT1 [7].

Other interactions of POLD1

• Thus, it was indicated that mutations in the MSH6 gene, and not in the POLD1 gene, are primarily responsible for the elevated mutation rates in DLD-1 cells [1].
• Most of transcripts involved in DNA repair were not detected but repression of POLD1 in the adult group and induction of XRCC5 and LIG4 were observed after UVA irradiation, as a function of age [8].
• Structure of the gene for the catalytic subunit of human DNA polymerase delta (POLD1) [9].

References