Rad51
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Recent papers in Rad51
Abstract: Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA... more
Abstract: Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell
signaling. They can also decrease DNA damage and promote cell survival. In the present study, we
demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes
but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in
a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan,
leading to an increase in cell survival and viability. The induction of RAD51A expression was in
response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin
pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of
RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA
damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest
that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A
pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and
cancer cells to polyamines may become the basis for the use of these compounds to protect normal
lymphocytes during lymphoblastic chemotherapy.
signaling. They can also decrease DNA damage and promote cell survival. In the present study, we
demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes
but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in
a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan,
leading to an increase in cell survival and viability. The induction of RAD51A expression was in
response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin
pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of
RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA
damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest
that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A
pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and
cancer cells to polyamines may become the basis for the use of these compounds to protect normal
lymphocytes during lymphoblastic chemotherapy.
- by Ekaterina Neborak and +1
- •
- Polyamines, Cytoprotection, Splicing, Rad51
The RAD51 gene encodes the protein that plays a central role in the repair of DNA double-strand breaks through the homologous recombination pathway. Association of RAD51 single nucleotide genetic polymorphism (SNP) with the development of... more
The RAD51 gene encodes the protein that plays a central role in the repair of DNA double-strand breaks through the homologous recombination pathway. Association of RAD51 single nucleotide genetic polymorphism (SNP) with the development of cancer has been observed to be tumor site- and race-specific. Thus, this study aimed to determine the potential association between RAD51 135G>C SNP and breast cancer among selected Filipinos. Patients with histologically confirmed breast cancer (n=60) seen at the University of Santo Tomas Hospital (Manila) were age- and sex-matched with clinically healthy controls (n=60). Genomic DNA was extracted from the blood of participants and analyzed for RAD51 genotype by polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP). A significantly higher incidence of RAD51 C/C genotype was seen among the cases than the controls (p<0.05). The more common G/C genotype was not associated with breast cancer development, while the recessive less common C/C genotype was observed to potentially increase the risk. However, passive smokers carrying the RAD51 G/C genotype had significantly increased chance of developing breast cancer. RAD51 G/C genotype even when combined with other established risk factors like alcohol use, active smoking, and family history were not associated with breast cancer.