Cloning and characterization of the<i>rad4</i>gene of<i>Schizosaccharomyces pombe</i>; a gene showing short regions of sequence similarity to the human XRCC1 gene

Fenech, Michael; Carr, Antony; Murray, Johanne M.; Watts, Felicity Z.; Lehmann, Alan R.

doi:10.1093/nar/19.24.6737

Cited by 69 publications

(37 citation statements)

References 22 publications

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“…Fission yeast has a single ortholog of each of Dpb11, Sld2, and Sld3, all of which are essential for chromosome replication (Fenech et al 1991;Nakajima and Masukata 2002;Noguchi et al 2002). Sld3 can associate with origins in the absence of CDK activity as in budding yeast, and is required for the subsequent recruitment of GINS and Cdc45 (Yabuuchi et al 2006).…”

Section: Sld2 and Sld3 Are The Major Targets For Cdk During The Initimentioning

confidence: 99%

How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?

Labib¹

2010

Genes Dev.

320

318

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Chromosome replication occurs precisely once during the cell cycle of almost all eukaryotic cells, and is a highly complex process that is still understood relatively poorly. Two conserved kinases called Cdc7 (cell division cycle 7) and cyclin-dependent kinase (CDK) are required to establish replication forks during the initiation of chromosome replication, and a key feature of this process is the activation of the replicative DNA helicase in situ at each origin of DNA replication. A series of recent studies has shed new light on the targets of Cdc7 and CDK, indicating that chromosome replication probably initiates by a fundamentally similar mechanism in all eukaryotes.

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Section: Sld2 and Sld3 Are The Major Targets For Cdk During The Initimentioning

confidence: 99%

How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?

Labib¹

2010

Genes Dev.

320

318

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“…TopBPl possessed eight repeating regions (regions 1 -8) similar to regions 1 and 2 of Rad4 protein (Fig. 3A), which repairs DNA damage by ultraviolet and radiation [13]. Rad4 is identical to Cut5, which is required for the onset of S phase and for the restraint of M phase before the completion of S phase [14].…”

Section: Sequence Of Topbplmentioning

confidence: 99%

A DNA‐Topoisomerase‐11–Binding Protein with Eight Repeating Regions Similar to DNA‐repair Enzymes and to a Cell‐Cycle Regulator

Yamane

Kawabata

Tsuruo

1997

European Journal of Biochemistry

106

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A two-hybrid system was used to isolate factors that interact with the C-terminal region of DNA topoisomerase IIP. A positive clone isolated from a HeLa cDNA library encoded 1.522 amino acid residues (molecular mass 170670). The protein, designated topoisomerase-ITP-binding protein 1 (TopBPl), interacted with the C-terminal region of topoisomerase IIP synthesized in vitw. A database search indicated that TopBPl possessed eight regions similar to regions of Rad4, Cut.5, Ect2, Revl and X-ray repair cross-complementing 1 (XRCC1) proteins and a region similar to auto-modification sites of poly(ADPribose) polymerase, suggesting that TopBPl supported catalytic reactions of topoisomerase I1 through transient breakages of DNA strands. . Therefore, a decrease in the number of cleavable complexes, including a reduction in enzyme quantity and activity, could confer drug resistance. Solid tumors that are naturally under stress conditions (e.g. hypoxia and glucose starvation) show a low amount of topoisomerase 11, which suggests that the resistance of solid tumors to chemotherapy is partly due to the decreased amount of topoisomerase I1 as the molecular target of major antitumor reagents [6, 71. To identify the factors involved in the regulatory mechanisms of topoisomerase I1 and to investigate the resistance mechanisms of solid tumors to chemotherapy, we adopted a twohybrid system [S], using the C-terminal region of human topoisomerase IIP. An isolated clone encoded eight repeating regions that are similar to the regions of Rad4, Cuts, Revl and X-ray repair cross-complementing (XRCC1) proteins, which are involved in DNA repair or regulation of the cell cycle. The protein, designated topoisomerase-binding protein 1 (TopBPl) contained a region similar to automodification sites of poly(ADPribose) polymerase, and may be involved in cell-cycle regulation and DNA repair, caused by failure of catalytic reactions of topoisomerase IT through DNA strand breaks. Keywords MATERIALS AND METHODSPlasmid construction. The C-terminal region of the human topoisomerase IlP gene [2] was amplified by PCR. The templates were cDNAs prepared from human kidney (Clontech, Quick-clone). Oligonucleotides used were 5'-GGATCCGGT-CAAAGAAAGATTTGAT-TCAAATG-3' and 5'-GATTTGTT-GAAAAATGTTTGTGCTC-3'. The region corresponding to amino acid 1143-1621 of topoisomerase Ilg was cloned into the BumH1-XhoI site of pEG202 [S], carrying the Zed gene to construct pK83.5 (a bait plasmid).Yeast two-hybrid system. The system was a kind gift of Dr Roger Brent, Harvard Medical School. Screening was performed according to his procedures [S]. Saccharumyces cer-evi.r.iue, ECY48 was transformed with pSH18-34 (a reporter) and pK83.5 (a bait). A HeLa cDNA expression library 181 was introduced into the transformants. After 2 days, approximately 10' independent clones which contained pSH18-34, pK835 and a cDNA plasmid, were replicated onto plates that lacked leucine but contained 5-broino-4-chloro-3-~ndoyl-~-~-galactopyranos~de and Dgalactose. A positive cDNA clone (termed pK835-5...

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“…Gene cloning of the cut5+ gene indicated that it was identical to the rad4+ gene previously reported by Fenech et al (1991). The rad4+ gene is one of many rad+ genes identified in fission yeast and is known to be required for the repair of X-ray-and UV-damaged DNA.…”

Section: Cell Division Block Produced By Uv Irradiationmentioning

confidence: 54%

“…The cut5+ gene encodes a putative 74 kDa (designated p74) polypeptide (Fenech et al, 1991;Saka and Yanagida, 1993;Lehmann, 1993). Close sequence alignment indicates that the protein product consists of four distinct domains: two repeti tive domains and two hydrophilic domains (Fig.…”

Section: The Product Of the Cut5+ Gene Is Similar To An Oncoproteinmentioning

confidence: 99%

“…Further more, cut5 mutations are radiation (UV and X-ray)-sensitive at the permissive temperature. Results of gene cloning indicated that the cut5+ gene is identical to rad4+, which was previously cloned and sequenced by Fenech et al (1991). The role of the cut5+ gene thus seemed intriguing, as it is impli cated in DNA replication/repair and in the restraint of mitosis/cytokinesis.…”

Section: Introductionmentioning

confidence: 99%

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Coupling of DNA replication and mitosis by fission yeast rad4/cut5

Saka

Fantes

Yanagida

1994

Journal of Cell Science

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SUMMARYThe fission yeast cut5+ (identical to rad4+) gene is essential for S phase. Its temperature-sensitive (ts) mutation causes mitosis while S phase is inhibited: dependence of mitosis upon the completion of S phase is abolished. If DNA is damaged in mutant cells, however, cell division is arrested. Thus the checkpoint control system for DNA damage is functional, while that for DNA synthesis inhibition is not in the cut5 mutants. Transcription of the cut5+ gene is not under the direct control of cdcl0+, which encodes a tran scription factor for the START of cell cycle. The transcript level does not change during the cell cycle. The protein product has four distinct domains and is enriched in the nucleus. Its level does not alter during the cell cycle. The N-domain is important for cut5 protein function: it is essential for complementation of ts cut5 mutations and its overexpression blocks cell division. Furthermore, it resembles the N-terminal repeat domain of proto-oncopro tein Ect2, which, in the C-domain, contains a regulator-like sequence for small G proteins. We discuss a hypothesis that the cut5 protein is an essential component of the checkpoint control system for the completion of DNA synthesis. The restraint of mitosis until the completion of S phase is mediated by the cut5 protein, which can sense the state of chromosome duplication and negatively interacts with M phase regulators such as cdc25 and cdc2.

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Cloning and characterization of therad4gene ofSchizosaccharomyces pombe; a gene showing short regions of sequence similarity to the human XRCC1 gene

Cited by 69 publications

References 22 publications

How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?

How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?

A DNA‐Topoisomerase‐11–Binding Protein with Eight Repeating Regions Similar to DNA‐repair Enzymes and to a Cell‐Cycle Regulator

Coupling of DNA replication and mitosis by fission yeast rad4/cut5

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