Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes.
Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA. thayerm@ohsu.edu
Mathew J
MJ
Thayer
D000818:Animals; D064127:Aurora Kinases; D043171:Chromosomal Instability; D002875:Chromosomes / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D042522:DNA Replication Timing; D003703:Demecolcine / Q000494:pharmacology; D006801:Humans; D008322:Mammals / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D018741:Replication Origin; D049951:X Chromosome Inactivation
D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D003703:Demecolcine