such as "Introduction", "Conclusion"..etc
Division of Molecular Medicine, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA
* To whom correspondence should be addressed. Tel: +1 5034942447; Fax: +1 5034947368; Email: [email protected]
Received June 13, 2005; Accepted August 10, 2005
An open article from Human Molecular Genetics 2005 14(19):2813-2827; doi:10.1093/hmg/ddi314.
Certain chromosome rearrangements, found in cancer cells orin cells exposed to ionizing radiation, exhibit a chromosome-widedelay in replication timing (DRT) that is associated with adelay in mitotic chromosome condensation (DMC). We have developeda chromosome engineering strategy that allows the generationof chromosomes with this DRT/DMC phenotype. We found that 10%of inter-chromosomal translocations induced by two distinctmechanisms, site-specific recombination mediated by Cre or non-homologousend joining of DNA double-strand breaks induced by I-Sce1, resultin DRT/DMC. Furthermore, on certain balanced translocationsonly one of the derivative chromosomes displays the phenotype.Finally, we show that the engineered DRT/DMC chromosomes acquiregross chromosomal rearrangements at an increased rate when comparedwith non-DRT/DMC chromosomes. These results indicate that theDRT/DMC phenotype is not the result of a stochastic processthat could occur at any translocation breakpoint or as an epigeneticresponse to chromosome damage. Instead, our data indicate thatthe replication timing of certain derivative chromosomes isregulated by a cis-acting mechanism that delays both initiationand completion of DNA synthesis along the entire length of thechromosome. Because chromosomes with DRT/DMC are common in tumorcells and in cells exposed to ionizing radiation, we proposethat DRT/DMC represents a common mechanism responsible for thegenomic instability found in cancer cells and for the persistentchromosomal instability associated with cells exposed to ionizingradiation.
Enter the code exactly as it appears. All letters are case insensitive, there is no zero.