Table 1. Genes participating in the repair of topoisomerase II mediated DNA damagea, b, c.
Gene | Function | Experimental system | Reference |
---|---|---|---|
Artemis | Nuclease participating in some NHEJ reactions | Mutant cell line | 145-147 |
ATM | Checkpoint signaling (Protein kinase) | Numerous | 9,125,148 |
ATR | Checkpoint signaling (Protein kinase) | Biochemical assay, chemical inhibition | 125,149,150 |
BRCA1 | Mutated in familial breast cancer, DNA damage sensing, transcription, possible modulator of Top2 activity | Mutant cell line | 71 |
BRCA2 | Mutated in familial breast cancer, homologous recombination, DNA repair DNA damage sensing | Mutant cell line | 71 |
CHK1 | Checkpoint signaling (Protein kinase) | Biochemical assay, siRNA | 150,151 |
CHK2 | Checkpoint signaling (Protein kinase) | Biochemical assay | 151,152 |
CtIP | BRCA1 binding protein that functions in the MEN pthway, nuclease, mammalian homolog of Sae2 | Biochemical assay | 64,153 |
DNA-PKcs | DNA dependent protein kinase catalytic subunit, required for NHEJ | Mutant cell line, siRNAd, chemical inhibition | 103,146,154,155 |
H2AX | Histone H2A isoform, phosphorylation marks double strand breaks | Mutant cell line | 156 |
KU70 | Subunit of a DNA binding complex (with DNA-PKcs required for NHEJ | Numerous | 154,157-159 |
KU80 | Subunit of a DNA binding complex (with DNA-PKcs required for NHEJ | Numerous | 154 |
LIG4 | DNA ligase IV, a ligase specific for NHEJ | siRNA | 155 |
MRE11 | Component of the MRN complex, required for DNA damage signaling and double strand break repair | Numerous | 160-162 |
NBS1 | Component of the MRN complex, required for DNA damage signaling and double strand break repair | Biochemical assay | 163,164 |
PLK1 | Polo-like kinase | Biochemical assay | 165 |
RAD50 | Component of the MRN complex, required for DNA damage signaling and double strand break repair | Biochemical assay | 166 |
RAD52 | Homologous recombination, repair of double strand breaks by homologous recombination | Yeast | 160,167,168 |
Rb1 | Retinoblastoma susceptibility protein, control of cell cycle progression | Mutant cell line | 169 |
TDP1 | Tyrosyl DNA phosphodiesterase I | Yeaste | 51,170 |
XPC | Nucleotide excision repair | siRNA | 155,171 |
XPG | Nucleotide excision repair | Yeastf | 51 |
Topoisomerase II targeting drugs have been frequently used in studying apoptosis. Therefore genes that affect sensitivity to Top2 targeting drugs mainly by affecting apoptosis are not included in this table.
Several genomic screens have been carried out using yeast to identify genes that confer sensitivity to Top2 targeting drugs 158,172,173. These genes have not been discussed here unless similar genes or processes have been identified in mammalian cells.
This table was assembled mainly using data using etoposide as a Top2 targeting drug. This was done to avoid the possible complication of effects of drugs (especially anthracyclines) on targets other than topoisomerase II.
Discordant results have been reported for the sensitivity of DNA-PKcs deficient cells to etoposide. More recently, a DNA-Pk inhibitor has been reported to confer sensitivity to etoposide 103.
Tdp1 mutants have been shown to confer sensitivity to etoposide in yeast cells, but not in mammalian cells.
Sensitivity to etoposide has been demonstrated in yeast rad2 mutants. RAD2 is the yeast homolog of XPG. Sensitivity of XPG mutants in mammalian cells has not been reported.