Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer.
Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbate...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3098187?pdf=render |
| _version_ | 1811268646058590208 |
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| author | Samah El Ghamrasni Ashwin Pamidi Marie Jo Halaby Miyuki Bohgaki Renato Cardoso Li Li Shriram Venkatesan Swaminathan Sethu Atsushi Hirao Tak W Mak Manoor Prakash Hande Anne Hakem Razqallah Hakem |
| author_facet | Samah El Ghamrasni Ashwin Pamidi Marie Jo Halaby Miyuki Bohgaki Renato Cardoso Li Li Shriram Venkatesan Swaminathan Sethu Atsushi Hirao Tak W Mak Manoor Prakash Hande Anne Hakem Razqallah Hakem |
| author_sort | Samah El Ghamrasni |
| collection | DOAJ |
| description | Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(Δex3-4/Δex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its predicted tumor suppressor function, loss of Chk2 promotes mitotic catastrophe and cell death, and it results in suppressed oncogenic transformation and tumor development in Mus81(Δex3-4/Δex3-4) background. Thus, our data indicate that an important role for Chk2 is maintaining lymphocyte development and that dual inactivation of Chk2 and Mus81 remarkably inhibits cancer. |
| first_indexed | 2024-04-12T21:27:52Z |
| format | Article |
| id | doaj.art-4957612603b249209a94c816b8eeda04 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-12T21:27:52Z |
| publishDate | 2011-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-4957612603b249209a94c816b8eeda042022-12-22T03:16:08ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-05-0175e100138510.1371/journal.pgen.1001385Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer.Samah El GhamrasniAshwin PamidiMarie Jo HalabyMiyuki BohgakiRenato CardosoLi LiShriram VenkatesanSwaminathan SethuAtsushi HiraoTak W MakManoor Prakash HandeAnne HakemRazqallah HakemChk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(Δex3-4/Δex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its predicted tumor suppressor function, loss of Chk2 promotes mitotic catastrophe and cell death, and it results in suppressed oncogenic transformation and tumor development in Mus81(Δex3-4/Δex3-4) background. Thus, our data indicate that an important role for Chk2 is maintaining lymphocyte development and that dual inactivation of Chk2 and Mus81 remarkably inhibits cancer.http://europepmc.org/articles/PMC3098187?pdf=render |
| spellingShingle | Samah El Ghamrasni Ashwin Pamidi Marie Jo Halaby Miyuki Bohgaki Renato Cardoso Li Li Shriram Venkatesan Swaminathan Sethu Atsushi Hirao Tak W Mak Manoor Prakash Hande Anne Hakem Razqallah Hakem Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. PLoS Genetics |
| title | Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. |
| title_full | Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. |
| title_fullStr | Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. |
| title_full_unstemmed | Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. |
| title_short | Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. |
| title_sort | inactivation of chk2 and mus81 leads to impaired lymphocytes development reduced genomic instability and suppression of cancer |
| url | http://europepmc.org/articles/PMC3098187?pdf=render |
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