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Article: Replication delay along FRA7H, a common fragile site on human chromosome 7, leads to chromosomal instability

TitleReplication delay along FRA7H, a common fragile site on human chromosome 7, leads to chromosomal instability
Authors
Issue Date2000
PublisherAmerican Society for Microbiology.
Citation
Molecular And Cellular Biology, 2000, v. 20 n. 12, p. 4420-4427 How to Cite?
AbstractCommon fragile sites are specific chromosomal loci that show gaps, breaks, or rearrangements in metaphase chromosomes under conditions that interfere with DNA replication. The mechanism underlying the chromosomal instability at fragile sites was hypothesized to associate with late replication time. Here, we aimed to investigate the replication pattern of the common fragile site FRA7H, encompassing 160 kb on the long arm of human chromosome 7. Using in situ hybridization on interphase nuclei, we revealed that the replication of this region is initiated relatively early, before 30% of S phase is completed. However, a high fraction (~35%) of S-phase nuclei showed allelic asynchrony, indicating that the replication of FRA7H is accomplished at different times in S phase. This allelic asynchrony is not the result of a specific replication time of each FRA7H allele. Analysis of the replication pattern of adjacent clones along FRA7H by using cell population and two-color fluorescent in situ hybridization analyses showed significant differences in the replication of adjacent clones, under normal growth condition and upon aphidicolin treatment. This pattern significantly differed from that of two nonfragile regions which showed a coordinated replication under both conditions. These results indicate that aphidicolin is enhancing an already existing difference in the replication time along the FRA7H region. Based on our replication analysis of FRA7H and on previous analysis of the common fragile site FRA3B, we suggest that delayed replication is underlying the fragility at aphidicolin-induced common fragile sites.
Persistent Identifierhttp://hdl.handle.net/10722/44360
ISSN
2015 Impact Factor: 4.427
2015 SCImago Journal Rankings: 3.806
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHellman, Aen_HK
dc.contributor.authorRahat, Aen_HK
dc.contributor.authorScherer, SWen_HK
dc.contributor.authorDarvasi, Aen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorKerem, Ben_HK
dc.date.accessioned2007-09-12T03:52:05Z-
dc.date.available2007-09-12T03:52:05Z-
dc.date.issued2000en_HK
dc.identifier.citationMolecular And Cellular Biology, 2000, v. 20 n. 12, p. 4420-4427en_HK
dc.identifier.issn0270-7306en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44360-
dc.description.abstractCommon fragile sites are specific chromosomal loci that show gaps, breaks, or rearrangements in metaphase chromosomes under conditions that interfere with DNA replication. The mechanism underlying the chromosomal instability at fragile sites was hypothesized to associate with late replication time. Here, we aimed to investigate the replication pattern of the common fragile site FRA7H, encompassing 160 kb on the long arm of human chromosome 7. Using in situ hybridization on interphase nuclei, we revealed that the replication of this region is initiated relatively early, before 30% of S phase is completed. However, a high fraction (~35%) of S-phase nuclei showed allelic asynchrony, indicating that the replication of FRA7H is accomplished at different times in S phase. This allelic asynchrony is not the result of a specific replication time of each FRA7H allele. Analysis of the replication pattern of adjacent clones along FRA7H by using cell population and two-color fluorescent in situ hybridization analyses showed significant differences in the replication of adjacent clones, under normal growth condition and upon aphidicolin treatment. This pattern significantly differed from that of two nonfragile regions which showed a coordinated replication under both conditions. These results indicate that aphidicolin is enhancing an already existing difference in the replication time along the FRA7H region. Based on our replication analysis of FRA7H and on previous analysis of the common fragile site FRA3B, we suggest that delayed replication is underlying the fragility at aphidicolin-induced common fragile sites.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology.en_HK
dc.relation.ispartofMolecular and Cellular Biologyen_HK
dc.rightsCopyright © American Society for Microbiology, Molecular and cellular biology, 2000, v. 20 n. 12, p. 4420-4427en_HK
dc.subject.meshChromosome fragilityen_HK
dc.subject.meshChromosomes, human, pair 7en_HK
dc.subject.meshDna replicationen_HK
dc.subject.meshChromosome fragile sitesen_HK
dc.subject.meshCell lineen_HK
dc.titleReplication delay along FRA7H, a common fragile site on human chromosome 7, leads to chromosomal instabilityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-7306&volume=20&issue=12&spage=4420&epage=4427&date=2000&atitle=Replication+delay+along+FRA7H,+a+common+fragile+site+on+human+chromosome+7,+leads+to+chromosomal+instabilityen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1128/MCB.20.12.4420-4427.2000en_HK
dc.identifier.pmid10825205-
dc.identifier.pmcidPMC85809-
dc.identifier.scopuseid_2-s2.0-0034117095en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034117095&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue12en_HK
dc.identifier.spage4420en_HK
dc.identifier.epage4427en_HK
dc.identifier.isiWOS:000087289700023-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHellman, A=7006735946en_HK
dc.identifier.scopusauthoridRahat, A=6602639524en_HK
dc.identifier.scopusauthoridScherer, SW=35374654500en_HK
dc.identifier.scopusauthoridDarvasi, A=7003374752en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridKerem, B=35376353800en_HK

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