Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines
Common genetic variants mapping to two distinct regions of RADS1B , a paralog of RADS1 , have been associated with breast cancer risk in genome-wide association studies (GWAS). RADS1B is a plausible candidate gene because of its established role in the homologous recombination (HR) process. How germ...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2014-01-01
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| Series: | Breast Cancer: Basic and Clinical Research |
| Online Access: | https://doi.org/10.4137/BCBCR.S17766 |
| _version_ | 1828436269921730560 |
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| author | Phoebe S. Lee Jun Fang Lea Jessop Timothy Myers Preethi Raj Nan Hu Chaoyu Wang Philip R. Taylor Jianjun Wang Javed Khan Maria Jasin Stephen J. Chanock |
| author_facet | Phoebe S. Lee Jun Fang Lea Jessop Timothy Myers Preethi Raj Nan Hu Chaoyu Wang Philip R. Taylor Jianjun Wang Javed Khan Maria Jasin Stephen J. Chanock |
| author_sort | Phoebe S. Lee |
| collection | DOAJ |
| description | Common genetic variants mapping to two distinct regions of RADS1B , a paralog of RADS1 , have been associated with breast cancer risk in genome-wide association studies (GWAS). RADS1B is a plausible candidate gene because of its established role in the homologous recombination (HR) process. How germline genetic variation in RADS1B confers susceptibility to breast cancer is not well understood. Here, we investigate the molecular function of RADS1B in breast cancer cell lines by knocking down RADS1B expression by small interfering RNA and treating cells with DNA-damaging agents, namely cisplatin, hydroxyurea, or methyl-methanesulfonate. Our results show that RAD51B -depleted breast cancer cells have increased sensitivity to DNA damage, reduced efficiency of HR, and altered cell cycle checkpoint responses. The influence of RAD51B on the cell cycle checkpoint is independent of its role in HR and further studies are required to determine whether these functions can explain the RADS1B breast cancer susceptibility alleles. |
| first_indexed | 2024-12-10T19:24:02Z |
| format | Article |
| id | doaj.art-0ea540d79eef40f18fbba5bfe7f1d86f |
| institution | Directory Open Access Journal |
| issn | 1178-2234 |
| language | English |
| last_indexed | 2024-12-10T19:24:02Z |
| publishDate | 2014-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Breast Cancer: Basic and Clinical Research |
| spelling | doaj.art-0ea540d79eef40f18fbba5bfe7f1d86f2022-12-22T01:36:24ZengSAGE PublishingBreast Cancer: Basic and Clinical Research1178-22342014-01-01810.4137/BCBCR.S17766Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell LinesPhoebe S. Lee0Jun Fang1Lea Jessop2Timothy Myers3Preethi Raj4Nan Hu5Chaoyu Wang6Philip R. Taylor7Jianjun Wang8Javed Khan9Maria Jasin10Stephen J. Chanock11Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Common genetic variants mapping to two distinct regions of RADS1B , a paralog of RADS1 , have been associated with breast cancer risk in genome-wide association studies (GWAS). RADS1B is a plausible candidate gene because of its established role in the homologous recombination (HR) process. How germline genetic variation in RADS1B confers susceptibility to breast cancer is not well understood. Here, we investigate the molecular function of RADS1B in breast cancer cell lines by knocking down RADS1B expression by small interfering RNA and treating cells with DNA-damaging agents, namely cisplatin, hydroxyurea, or methyl-methanesulfonate. Our results show that RAD51B -depleted breast cancer cells have increased sensitivity to DNA damage, reduced efficiency of HR, and altered cell cycle checkpoint responses. The influence of RAD51B on the cell cycle checkpoint is independent of its role in HR and further studies are required to determine whether these functions can explain the RADS1B breast cancer susceptibility alleles.https://doi.org/10.4137/BCBCR.S17766 |
| spellingShingle | Phoebe S. Lee Jun Fang Lea Jessop Timothy Myers Preethi Raj Nan Hu Chaoyu Wang Philip R. Taylor Jianjun Wang Javed Khan Maria Jasin Stephen J. Chanock Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines Breast Cancer: Basic and Clinical Research |
| title | Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines |
| title_full | Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines |
| title_fullStr | Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines |
| title_full_unstemmed | Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines |
| title_short | Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines |
| title_sort | activity and cell cycle regulation in response to dna damage in breast cancer cell lines |
| url | https://doi.org/10.4137/BCBCR.S17766 |
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