ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair.
DNA replication fork stalling or collapse that arises from endogenous damage poses a serious threat to genome stability, but cells invoke an intricate signaling cascade referred to as the DNA damage response (DDR) to prevent such damage. The gene product ataxia telangiectasia and Rad3-related (ATR)...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091222&type=printable |
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| _version_ | 1850024131698884608 |
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| author | Adam D Brown Brian W Sager Aparna Gorthi Sonal S Tonapi Eric J Brown Alexander J R Bishop |
| author_facet | Adam D Brown Brian W Sager Aparna Gorthi Sonal S Tonapi Eric J Brown Alexander J R Bishop |
| author_sort | Adam D Brown |
| collection | DOAJ |
| description | DNA replication fork stalling or collapse that arises from endogenous damage poses a serious threat to genome stability, but cells invoke an intricate signaling cascade referred to as the DNA damage response (DDR) to prevent such damage. The gene product ataxia telangiectasia and Rad3-related (ATR) responds primarily to replication stress by regulating cell cycle checkpoint control, yet it's role in DNA repair, particularly homologous recombination (HR), remains unclear. This is of particular interest since HR is one way in which replication restart can occur in the presence of a stalled or collapsed fork. Hypomorphic mutations in human ATR cause the rare autosomal-recessive disease Seckel syndrome, and complete loss of Atr in mice leads to embryonic lethality. We recently adapted the in vivo murine pink-eyed unstable (pun) assay for measuring HR frequency to be able to investigate the role of essential genes on HR using a conditional Cre/loxP system. Our system allows for the unique opportunity to test the effect of ATR loss on HR in somatic cells under physiological conditions. Using this system, we provide evidence that retinal pigment epithelium (RPE) cells lacking ATR have decreased density with abnormal morphology, a decreased frequency of HR and an increased level of chromosomal damage. |
| format | Article |
| id | doaj-art-8b467f06cfef4ff69970e31aa3123155 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8b467f06cfef4ff69970e31aa31231552025-08-20T03:01:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9122210.1371/journal.pone.0091222ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair.Adam D BrownBrian W SagerAparna GorthiSonal S TonapiEric J BrownAlexander J R BishopDNA replication fork stalling or collapse that arises from endogenous damage poses a serious threat to genome stability, but cells invoke an intricate signaling cascade referred to as the DNA damage response (DDR) to prevent such damage. The gene product ataxia telangiectasia and Rad3-related (ATR) responds primarily to replication stress by regulating cell cycle checkpoint control, yet it's role in DNA repair, particularly homologous recombination (HR), remains unclear. This is of particular interest since HR is one way in which replication restart can occur in the presence of a stalled or collapsed fork. Hypomorphic mutations in human ATR cause the rare autosomal-recessive disease Seckel syndrome, and complete loss of Atr in mice leads to embryonic lethality. We recently adapted the in vivo murine pink-eyed unstable (pun) assay for measuring HR frequency to be able to investigate the role of essential genes on HR using a conditional Cre/loxP system. Our system allows for the unique opportunity to test the effect of ATR loss on HR in somatic cells under physiological conditions. Using this system, we provide evidence that retinal pigment epithelium (RPE) cells lacking ATR have decreased density with abnormal morphology, a decreased frequency of HR and an increased level of chromosomal damage.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091222&type=printable |
| spellingShingle | Adam D Brown Brian W Sager Aparna Gorthi Sonal S Tonapi Eric J Brown Alexander J R Bishop ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. PLoS ONE |
| title | ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. |
| title_full | ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. |
| title_fullStr | ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. |
| title_full_unstemmed | ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. |
| title_short | ATR suppresses endogenous DNA damage and allows completion of homologous recombination repair. |
| title_sort | atr suppresses endogenous dna damage and allows completion of homologous recombination repair |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091222&type=printable |
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