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. Author manuscript; available in PMC: 2009 Nov 1.
Published in final edited form as: Nat Rev Cancer. 2009 Apr 20;9(5):338–350. doi: 10.1038/nrc2607

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
a

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.

b

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.

c

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.

d

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.

e

Tdp1 mutants have been shown to confer sensitivity to etoposide in yeast cells, but not in mammalian cells.

f

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.