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Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene

Digweed, M. and Günthert, U. and Schneider, R. and Seyschab, H. and Friedl, R. and Sperling, K.. (1995) Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene. Molecular and cellular biology, Vol. 15, H. 1. S. 305-314.

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Official URL: http://edoc.unibas.ch/dok/A5249238

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Abstract

Primary fibroblasts from patients with the genetic disease Fanconi anemia, which are hypersensitive to cross-linking agents, were used to screen a cDNA library for sequences involved in their abnormal cellular response to a cross-linking challenge. By using library partition and microinjection of in vitro-transcribed RNA, a cDNA clone, pSPHAR (S-phase response), which is able to correct the permanent repression of semiconservative DNA synthesis rates characteristic of these cells, was isolated. Wild-type SPHAR mRNA is expressed in all fibroblasts so far analyzed, including those of Fanconi anemia patients. Correction of the abnormal response in these cells appears therefore to be due to overexpression after cDNA transfer rather than to genetic complementation. The cDNA contains an open reading frame coding for a polypeptide of 7.5 kDa. Rabbit antiserum directed against a SPHAR peptide detects a protein of 7.9 kDa in Western blots (immunoblots) of whole-cell extracts from proliferating, but not resting, fibroblasts. The deduced amino acid sequence of SPHAR contains a motif found in the cyclins, and it is proposed that SPHAR acts within the injected cell by interfering with the cyclin-controlled maintenance of S phase. In agreement with this proposal, normal cells transfected with an antisense SPHAR expression vector have a significantly reduced rate of DNA synthesis during S phase and a prolonged G2 phase, reflecting the need for postreplicative DNA processing before entry into mitosis.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Allgemeine Pathologie (Tolnay)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Allgemeine Pathologie (Tolnay)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Allgemeine und spezielle Pathologie (Oberholzer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Allgemeine und spezielle Pathologie (Oberholzer)
UniBasel Contributors:Günthert, Ursula
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5549
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Last Modified:31 Dec 2015 10:44
Deposited On:22 Mar 2012 13:34

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