Evidence for two senescence loci on human chromosome I

✍ Scribed by Patrick J. Vojta; P. Andrew Futreal; Lois A. Annab; Hidenori Kato; Olivia M. Pereira-Smith; J. Carl Barrett

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 872 KB
• Volume: 16
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199605)16:1<55::aid-gcc8>3.0.co;2-2

✦ Synopsis

Microcell-mediated introduction of a neo-tagged human chromosome I (HC-I-neo) into several immortal cell lines has previously been shown to induce growth arrest and phenotypic changes indicative of replicative senescence. Somatic cell hybridization studies have localized senescence activity for immortal hamster I OW-2 cells to a cytogenetically defined region between I q23 and the q terminus. Previous microcell-mediated chromosome transfer experiments showed that a chromosome I with an interstitial q-arm deletion (del-I q) lacks senescence inducing activity for several immortal human cell lines that are sensitive to an intact HC-I -neo. In contrast, our studies reveal that the del-I q chromosome retains activity for I OW-2 cells, indicating that there are at least two senescence genes on human chromosome I. Sequence-tagged site (STS) content analysis revealed that the q arm of the del-I q chromosome has an interstitial deletion of approximately 63 centimorgans (cM), between the proximal STS marker D I S534 and distal marker D I S4 12. approximately I q I 2 to I q3 I. This deletion analyxis provides a candidate region for one of the senescence genes on I q. In addition, because this deletion region extends distally beyond I q23. it localizes the region containing a second senescence gene to approximately I q3 I -qter, between D I S422 and the q terminus. STS content analysis of a panel of I I I OW-2 microcell hybrid clones that escaped senescence identified 2 common regions of loss of I q material below the distal breakpoint of del-I q. One region is flanked by markers D I S459 and ACTN2, and the second lies between markers Wl-4683 and D I S 1609, indicating that the distal I q senescence gene(s) localizes within I q42-43. Genes