C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability
DNA replication and its connection to M phase restraint are studied extensively at the level of single cells but rarely in the context of a developing animal. C. elegans lin-6 mutants lack DNA synthesis in postembryonic somatic cell lineages, while entry into mitosis continues. These mutants grow sl...
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| Format: | Article |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92333 https://orcid.org/0000-0002-9964-9613 |
| _version_ | 1811084634831716352 |
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| author | Korzelius, Jerome The, Inge Ruijtenberg, Suzan Portegijs, Vincent Xu, Huihong van den Heuvel, Sander Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Korzelius, Jerome The, Inge Ruijtenberg, Suzan Portegijs, Vincent Xu, Huihong van den Heuvel, Sander Horvitz, Howard Robert |
| author_sort | Korzelius, Jerome |
| collection | MIT |
| description | DNA replication and its connection to M phase restraint are studied extensively at the level of single cells but rarely in the context of a developing animal. C. elegans lin-6 mutants lack DNA synthesis in postembryonic somatic cell lineages, while entry into mitosis continues. These mutants grow slowly and either die during larval development or develop into sterile adults. We found that lin-6 corresponds to mcm-4 and encodes an evolutionarily conserved component of the MCM2-7 pre-RC and replicative helicase complex. The MCM-4 protein is expressed in all dividing cells during embryonic and postembryonic development and associates with chromatin in late anaphase. Induction of cell cycle entry and differentiation continues in developing mcm-4 larvae, even in cells that went through abortive division. In contrast to somatic cells in mcm-4 mutants, the gonad continues DNA replication and cell division until late larval development. Expression of MCM-4 in the epidermis (also known as hypodermis) is sufficient to rescue the growth retardation and lethality of mcm-4 mutants. While the somatic gonad and germline show substantial ability to cope with lack of zygotic mcm-4 function, mcm-4 is specifically required in the epidermis for growth and survival of the whole organism. Thus, C. elegans mcm-4 has conserved functions in DNA replication and replication checkpoint control but also shows unexpected tissue-specific requirements. |
| first_indexed | 2024-09-23T12:54:41Z |
| format | Article |
| id | mit-1721.1/92333 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:54:41Z |
| publishDate | 2014 |
| publisher | Elsevier |
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| spelling | mit-1721.1/923332022-10-01T11:49:40Z C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability Korzelius, Jerome The, Inge Ruijtenberg, Suzan Portegijs, Vincent Xu, Huihong van den Heuvel, Sander Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Horvitz, H. Robert DNA replication and its connection to M phase restraint are studied extensively at the level of single cells but rarely in the context of a developing animal. C. elegans lin-6 mutants lack DNA synthesis in postembryonic somatic cell lineages, while entry into mitosis continues. These mutants grow slowly and either die during larval development or develop into sterile adults. We found that lin-6 corresponds to mcm-4 and encodes an evolutionarily conserved component of the MCM2-7 pre-RC and replicative helicase complex. The MCM-4 protein is expressed in all dividing cells during embryonic and postembryonic development and associates with chromatin in late anaphase. Induction of cell cycle entry and differentiation continues in developing mcm-4 larvae, even in cells that went through abortive division. In contrast to somatic cells in mcm-4 mutants, the gonad continues DNA replication and cell division until late larval development. Expression of MCM-4 in the epidermis (also known as hypodermis) is sufficient to rescue the growth retardation and lethality of mcm-4 mutants. While the somatic gonad and germline show substantial ability to cope with lack of zygotic mcm-4 function, mcm-4 is specifically required in the epidermis for growth and survival of the whole organism. Thus, C. elegans mcm-4 has conserved functions in DNA replication and replication checkpoint control but also shows unexpected tissue-specific requirements. 2014-12-16T18:06:39Z 2014-12-16T18:06:39Z 2010-12 2010-11 Article http://purl.org/eprint/type/JournalArticle 00121606 1095-564X http://hdl.handle.net/1721.1/92333 Korzelius, Jerome, Inge The, Suzan Ruijtenberg, Vincent Portegijs, Huihong Xu, H. Robert Horvitz, and Sander van den Heuvel. “C. Elegans MCM-4 Is a General DNA Replication and Checkpoint Component with an Epidermis-Specific Requirement for Growth and Viability.” Developmental Biology 350, no. 2 (February 2011): 358–369. © 2010 Elsevier Inc. https://orcid.org/0000-0002-9964-9613 en_US http://dx.doi.org/10.1016/j.ydbio.2010.12.009 Developmental Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Korzelius, Jerome The, Inge Ruijtenberg, Suzan Portegijs, Vincent Xu, Huihong van den Heuvel, Sander Horvitz, Howard Robert C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title | C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title_full | C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title_fullStr | C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title_full_unstemmed | C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title_short | C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability |
| title_sort | c elegans mcm 4 is a general dna replication and checkpoint component with an epidermis specific requirement for growth and viability |
| url | http://hdl.handle.net/1721.1/92333 https://orcid.org/0000-0002-9964-9613 |
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