A mortality gene(s) for the human adenocarcinoma line HeLa maps to a 130-kb region of human chromosome 4q22-q23.
Human chromosome 4 was previously shown to elicit features of senescence when introduced into cell lines that map to complementation group B for senescence, including HeLa cells. Subsequently, a DNA segment encoding the pseudogene Mortality Factor 4 (MORF4) was shown to reproduce some of the effects of the intact chromosome 4 and was suggested to be a candidate mortality gene. We have identified multiple MORF4 alleles in several cell lines and tissues by sequencing and have failed to detect any cancer-specific mutations in three of the complementation group B lines (HeLa, T98G, and J82). Furthermore, MORF4 was heterozygous in these lines. These results question whether MORF4 is the chromosome 4 mortality gene. To map other candidate mortality gene(s) on this chromosome, we employed microcell-mediated monochromosome transfer to introduce either a complete copy, or defined fragments of the chromosome into HeLa cells. The introduced chromosome 4 fragments mapped the mortality gene to a region between the centromere and the marker D4S2975 (4q27), thus excluding MORF4, which maps to 4q33-q34.1. Analysis of microsatellite markers on the introduced chromosome in 59 immortal segregants identified a frequently deleted region, spanning the markers BIR0110 and D4S1557. This defines a new candidate interval of 130 kb at 4q22-q23.
Bryce
Steven D
SD
Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.
Morrison
Vivienne
V
Craig
Nicola J
NJ
Forsyth
Nicholas R
NR
Fitzsimmons
Sara A
SA
Ireland
Hazel
H
Cuthbert
Andrew P
AP
Newbold
Robert F
RF
Parkinson
E Kenneth
EK
D000483:Alleles; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D002874:Chromosome Mapping; D020223:Chromosome Painting; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics* / Q000378:metabolism; D002999:Clone Cells; D016147:Genes, Tumor Suppressor; D005816:Genetic Complementation Test; D005838:Genotype; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D018895:Microsatellite Repeats; D010641:Phenotype; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C109882:MORF4 protein, human; D014157:Transcription Factors