TY  - GEN
AB  - A subset of tumor-derived chromosomal rearrangements exhibits delayed replication timing (DRT) and delayed mitotic chromosome condensation (DMC), leading to genomic instability and a markedly increased rate of new chromosomal rearrangements. Using site-specific recombination-mediated chromosome engineering, we identified a cis-acting locus on human chromosome 6 that regulates replication timing across the entire chromosome. Disruption of this locus induces chromosome-wide replication delay and reactivates previously silent alleles of mono-allelically expressed genes. This region contains a large intergenic non-coding RNA, named ASAR6 (asynchronous replication and autosomal RNA on chromosome 6), which replicates asynchronously in coordination with other mono-allelically expressed genes. These findings reveal that human autosomes harbor discrete loci controlling replication timing, mono-allelic expression, and chromosome stability. Alterations in such loci may contribute to genomic instability observed in cancer and following ionizing radiation exposure.
AD  - Oregon Health and Science University
AU  - Stoffregen, Eric
DA  - 2011
DO  - 10.6083/M4TD9V96
DO  - DOI
ED  - Thayer, Mathew
ED  - Mentor
ID  - 604
KW  - DNA Replication Timing
KW  - RNA
KW  - Genomic Instability
KW  - Chromosomes, Human, Pair 6
KW  - Neoplasms
KW  - Chromosomal Instability
KW  - RNA, Untranslated
KW  - asynchronous replication
KW  - mono-allelic expression
L1  - https://digitalcollections.ohsu.edu/record/604/files/605_etd.pdf
L2  - https://digitalcollections.ohsu.edu/record/604/files/605_etd.pdf
L4  - https://digitalcollections.ohsu.edu/record/604/files/605_etd.pdf
LK  - https://digitalcollections.ohsu.edu/record/604/files/605_etd.pdf
N2  - A subset of tumor-derived chromosomal rearrangements exhibits delayed replication timing (DRT) and delayed mitotic chromosome condensation (DMC), leading to genomic instability and a markedly increased rate of new chromosomal rearrangements. Using site-specific recombination-mediated chromosome engineering, we identified a cis-acting locus on human chromosome 6 that regulates replication timing across the entire chromosome. Disruption of this locus induces chromosome-wide replication delay and reactivates previously silent alleles of mono-allelically expressed genes. This region contains a large intergenic non-coding RNA, named ASAR6 (asynchronous replication and autosomal RNA on chromosome 6), which replicates asynchronously in coordination with other mono-allelically expressed genes. These findings reveal that human autosomes harbor discrete loci controlling replication timing, mono-allelic expression, and chromosome stability. Alterations in such loci may contribute to genomic instability observed in cancer and following ionizing radiation exposure.
PB  - Oregon Health and Science University
PY  - 2011
T1  - Genetic analysis of chromosome replication timing: an autosomal locus that controls chromosome-wide replication timing and mono-allelic expression
TI  - Genetic analysis of chromosome replication timing: an autosomal locus that controls chromosome-wide replication timing and mono-allelic expression
UR  - https://digitalcollections.ohsu.edu/record/604/files/605_etd.pdf
Y1  - 2011
ER  -