Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the Bloom syndrome helicase BLM.
The Bloom syndrome helicase BLM and the tumor-suppressor protein p53 play important roles in preserving genome integrity. Here, we knock out the genes for BLM and p53 in a human pre-B-cell line, Nalm-6. We show that p53 plays an important role in cell proliferation, but not apoptosis, when BLM is absent. Intriguingly, despite the apoptotic function of p53, BLM(/)TP53(/) cells were more sensitive than either single mutant to etoposide, an anticancer agent that poisons DNA topoisomerase II. Our results suggest a direct, BLM-independent role for p53 in etoposide-induced, topoisomerase II-mediated DNA damage in human cells.
So
Sairei
S
Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan.
Adachi
Noritaka
N
Koyama
Hideki
H
D001816:Bloom Syndrome / Q000201:enzymology / Q000235:genetics*; D002455:Cell Division; D002460:Cell Line; D004265:DNA Helicases / Q000172:deficiency*; D004260:DNA Repair; D005047:Etoposide / Q000633:toxicity*; D017353:Gene Deletion; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D012854:Sister Chromatid Exchange; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D004265:DNA Helicases