Graduate Studies Faculty
Mathew Thayer, PhD
Programs:Biochemistry & Molecular Biology
Molecular & Medical Genetics
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Research Interests:Chromosome Structure Genome stability cell cycle checkpoints DNA replication; cellular; medical » PubMed Listing
Preceptor RotationsDr. Thayer has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Thayer might be available as a mentor for 2015-2016.
Mammalian cells initiate DNA replication at multiple sites along each chromosome at different times, following a temporal replication program. The Thayer lab has characterized an abnormal chromosomal phenotype, which is exemplified by delayed replication timing, delayed mitotic chromosome condensation and structural instability of the affected chromosomes. We used a series of genetic approaches to identify and characterize discrete cis-acting loci responsible for this abnormal chromosomal phenotype. We found that Cre/loxP-mediated translocations, affecting eight different autosomes, display a delay in replication timing and structural instability of entire chromosomes. Subsequently, we found that Cre/loxP-mediated disruption of the lncRNA genes ASAR6 and ASAR15 result in delayed replication of human chromosomes 6 and 15, respectively. ASAR6 and ASAR15 share numerous characteristics with Xist, including: 1) random mono-allelic expression of lncRNAs that can physically “coat” entire chromosomes in cis; 2) asynchronous replication between alleles; 3) genetic disruption results in structural instability of their respective chromosomes; and 4) ectopic integration of transgenes causes delayed replication and transcriptional silencing of entire chromosomes. In earlier studies, we detected the delayed replication and structural instability phenotypes following rearrangement of numerous human and mouse chromosomes, suggesting that all mammalian chromosomes are regulated by similar mechanisms. Our work, combined with the observation that disruption of Xist results in a phenocopy of the delayed replication and instability phenotype caused by disruption of either ASAR6 or ASAR15, suggests that all mammalian chromosomes are regulated by similar loci.Therefore, we are proposing that all mammalian chromosomes contain “inactivation/stability centers” (I/SCs), which normally function to promote proper replication timing, monoallelic gene expression and structural stability of individual chromosomes. We believe that I/SCs are as fundamentally important to mammalian chromosome biology as telomeres, centromeres, or origins of replication.Thus, under this scenario every mammalian chromosome contains four essential cis-acting elements, origins, centromeres, telomeres, and I/SCs all functioning to ensure proper replication, segregation and stability of each chromosome.
Kevin S. Breger, Leslie Smith, Mitchell S. Turker, and Mathew J. Thayer. (2004). Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation. Cancer Research, 64, 8231–38.
Breger, K. S., Smith, L. G., and Thayer, M. J. Engineering Translocations with Delayed Replication Timing: Evidence for cis Control of Replication Timing. (2005). Hum Mol Genet. 14: 2813-27.
Chang, B.H., Smith, L., Huang, J. and Thayer, M. Chromosomes with delayed replication timing lead to checkpoint activation, delayed recruitment of Aurora B and chromosome instability. (2006) Oncogene, Sep 25; [Epub ahead of print].
Stoffregen, E.P, Donley, N, Stauffer, D, Smith, L and Thayer, MJ. An Autosomal Locus that Controls Chromosome-wide Replication Timing and Mono-Allelic Expression. (2011) Hum Mol Gen 20:2366-78.
Thayer, MJ. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation and stability of entire chromosomes. Bioessays. (2012) 34:760-70.
Donley N., Stoffregen E.P., Smith L., Montagna C., Thayer M.J. Asynchronous Replication, Mono-Allelic Expression, and Long Range-Effects of ASAR6. PLoS Genet (2013) 9:Epub 2013 Apr 4.
Donley, N., Smith L., and Thayer M.J. ASAR15, A cis-Acting Locus that Controls Chromosome-Wide Replication Timing and Stability of Human Chromosome 15. PLoS Genet (2015) 11: e1004923.
Graduate Education: University of Southern California; Department of Microbiology; Los Angeles, CA; Graduated June, 1988; Doctor of Philosophy in Microbiology; Dr. R.E.K. Fournier, PhD, advisor