The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication
Open accessAbstract
The six main minichromosome maintenance proteins (Mcm2–7), which presumably constitute the core of the replicative DNA helicase, are present in chromatin in large excess relative to the number of active replication forks. To evaluate the relevance of this apparent surplus of Mcm2–7 complexes in human cells, their levels were down-regulated by using RNA interference. Interestingly, cells continued to proliferate for several days after the acute (>90%) reduction of Mcm2–7 concentration. However, they became hypersensitive to DNA replication stress, accumulated DNA lesions, and eventually activated a checkpoint response that prevented mitotic division. When this checkpoint was abrogated by the addition of caffeine, cells quickly lost viability, and their karyotypes revealed striking chromosomal aberrations. Single-molecule analyses revealed that cells with a reduced concentration of Mcm2–7 complexes display normal fork progression but have lost the potential to activate “dormant” origins that serve a backup function during DNA replication. Our data show that the chromatin-bound “excess” Mcm2–7 complexes play an important role in maintaining genomic integrity under conditions of replicative stress.
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Cites
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre’, M., Giovanni Nuciforo, P., Bensimon, A., et al. (2006) · Nature · doi:10.1038/nature05327 · Cited by 1,821
To cycle or not to cycle: a critical decision in cancer
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Self-citationMoyer, S. E., Lewis, P. W., & Botchan, M. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602400103 · Cited by 699
Deregulated cyclin E induces chromosome instability
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Dynamic Molecular Combing: Stretching the Whole Human Genome for High-Resolution Studies
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Dormant origins licensed by excess Mcm2–7 are required for human cells to survive replicative stress
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Syljuåsen, R. G., Sørensen, C. S., Hansen, L. T., Fugger, K., Lundin, C., Johansson, F., Helleday, T., Sehested, M., Lukas, J., & Bartek, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.9.3553-3562.2005 · Cited by 550
Cell Cycle Regulation of DNA Replication
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Replication protein A-mediated recruitment and activation of Rad17 complexes
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Cited by
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Maintaining genome stability at the replication fork
Branzei, D., & Foiani, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2852 · Cited by 786
Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells
Flach, J., Bakker, S. T., Mohrin, M., Conroy, P. C., Pietras, E. M., Reynaud, D., Alvarez, S., Diolaiti, M. E., Ugarte, F., Forsberg, E. C., et al. (2014) · Nature · doi:10.1038/nature13619 · Cited by 650
Self-citationThe role of nuclear lamin B1 in cell proliferation and senescence
Shimi, T., Butin-Israeli, V., Adam, S. A., Hamanaka, R. B., Goldman, A. E., Lucas, C. A., Shumaker, D. K., Kosak, S. T., Chandel, N. S., & Goldman, R. D. (2011) · Genes & Development · doi:10.1101/gad.179515.111 · Cited by 547
Aguilera, A., & García-Muse, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133232 · Cited by 476
Metadata
- Authors
- Ibarra, A., Schwob, E., & Méndez, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-07
- Volume
- 105
- Issue
- 26
- Pages
- 8956-8961
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2162221778
- Cited by
- 503
- References
- 32
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- green
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- Ibarra, A., Schwob, E., & Méndez, J. (2008). Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0803978105
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