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, A -Acting Locus that Controls Chromosome-Wide Replication Timing and Stability of Human Chromosome 15


Mammalian cells replicate their DNA along each chromosome during a precise temporal replication program. In this report, we used a novel “chromosome-engineering” strategy to identify a DNA element that controls this replication-timing program of human chromosome 15. Characterization of this element indicated that it encodes large non-protein-coding RNAs that are retained in the nucleus and form a “cloud” on one copy of chromosome 15. Previously, we found that structural rearrangements of a similar element on human chromosome 6 causes delayed replication and structural instability of chromosome 6. Mammalian chromosomes are known to contain three distinct types of essential DNA elements that promote proper chromosome function. Thus, every chromosome contains: 1) origins of replication, which are responsible for proper initiation of DNA synthesis; 2) centromeres, which are responsible for proper chromosome separation during cell division; and 3) telomeres, which are responsible for replication and protection of the ends of linear chromosomes. Our work supports a model in which all mammalian chromosomes contain a fourth type of essential DNA element, the “inactivation/stability center”, which is responsible for proper DNA replication timing and structural stability of each chromosome.


Vyšlo v časopise: , A -Acting Locus that Controls Chromosome-Wide Replication Timing and Stability of Human Chromosome 15. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004923
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004923

Souhrn

Mammalian cells replicate their DNA along each chromosome during a precise temporal replication program. In this report, we used a novel “chromosome-engineering” strategy to identify a DNA element that controls this replication-timing program of human chromosome 15. Characterization of this element indicated that it encodes large non-protein-coding RNAs that are retained in the nucleus and form a “cloud” on one copy of chromosome 15. Previously, we found that structural rearrangements of a similar element on human chromosome 6 causes delayed replication and structural instability of chromosome 6. Mammalian chromosomes are known to contain three distinct types of essential DNA elements that promote proper chromosome function. Thus, every chromosome contains: 1) origins of replication, which are responsible for proper initiation of DNA synthesis; 2) centromeres, which are responsible for proper chromosome separation during cell division; and 3) telomeres, which are responsible for replication and protection of the ends of linear chromosomes. Our work supports a model in which all mammalian chromosomes contain a fourth type of essential DNA element, the “inactivation/stability center”, which is responsible for proper DNA replication timing and structural stability of each chromosome.


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