Positions
- Associate Professor
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Molecular and Human Genetics
ÌÇÐÄÊÓƵ of Medicine
Houston, TX, US
- Associate Professor
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Molecular Virology & Microbiology
ÌÇÐÄÊÓƵ of Medicine
Houston, Texas, United States
- Associate Professor
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Program in Integrative Molecular and Biomedical Sciences
ÌÇÐÄÊÓƵ of Medicine
Houston, Texas, United States
- Member
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Dan L Duncan Cancer Center
ÌÇÐÄÊÓƵ of Medicine
Education
- PhD from University of New Mexico
- 01/1998 - Albuquerque, New Mexico, United States
- Post-Doctoral Fellowship at Harvard University
- 01/2006 - Cambridge, Massachusetts, United States
Honors & Awards
- Fulbright & Jaworski L.L.P Teaching Award
- ÌÇÐÄÊÓƵ of Medicine (05/2015)
Professional Interests
- Chromosome dynamics, molecular mechanisms of DNA replication, and cell cycle control in E. coli
Professional Statement
Chromosome Dynamics: Although genetic information is encoded in a one-dimensional array of DNA bases, all major DNA processes (replication, transcription and recombination) are controlled by changes in the three-dimensional structure of DNA. Large-scale structural features of chromosomes including the arrangement of important chromosomal sites (origins, termini and centromeres) and overall chromosome compactness change dramatically and predictably during the cell cycle. However, these features are difficult to measure using standard microscopy methods. Our lab is developing a novel chromosome painting technology to image individual domains within the entire chromosome in single bacterial cells. This method, inspired by in situ hybridization-based human karyotyping techniques, utilizes multi-color combinatorial labeling and high resolution three-dimensional photography to generate whole genome maps of the chromosome. Our goal is to define the cell cycle program of chromosome movement in E. coli using a cell cycle synchronization apparatus we designed called the “baby cell machine."
Chromosome Cohesion: In eukaryotes, replicated chromosomes are held together by linkages (cohesion) until they are separated by the mitotic spindle apparatus. Our lab showed that an analogous cohesion process occurs in bacteria, in which replicated DNA is linked together as it exits the replication fork, remaining stably attached for 10-20 minutes before segregating apart. Evidence suggests that bacterial cohesion is not protein (glue) based, but rather results from entanglement of sister chromosomes in a topological structure called a precatenane. Interestingly, cohesion occurs much more strongly in some regions of the E. coli chromosome, which we refer to as “snaps." We are currently exploring models of how these centromere-like snaps are generated and what role they play in faithful chromosome replication, repair and segregation.
DNA Replication: In vitro, precatenanes form along DNA segments that are under positive helical tension (overwound). The presence of precatenanes behind replication forks in vivo implies that replicative helicases generate tension that outpaces the relaxing ability of topoisomerases (forks can travel at an astounding 1000 bp/sec!). Theoretically, this tension rapidly spins the replication fork causing the two replicated DNAs to wrap around each other. Our lab is investigating whether DNA-bound proteins act as topological barriers during replication, driving the formation of precatenanes. The basic enzymology of DNA replication is well conserved among all life, and it has recently been shown that eukaryotic chromosomes are also highly catenated along their lengths.
We expect that our work will lead to a better understanding of the factors that limit replication fork speed, cause replication fork stalling (quickly leading to double-strand breaks), and inhibit chromosome segregation. These events in humans are a major source of genomic instability and diseases including cancer.
Chromosome Cohesion: In eukaryotes, replicated chromosomes are held together by linkages (cohesion) until they are separated by the mitotic spindle apparatus. Our lab showed that an analogous cohesion process occurs in bacteria, in which replicated DNA is linked together as it exits the replication fork, remaining stably attached for 10-20 minutes before segregating apart. Evidence suggests that bacterial cohesion is not protein (glue) based, but rather results from entanglement of sister chromosomes in a topological structure called a precatenane. Interestingly, cohesion occurs much more strongly in some regions of the E. coli chromosome, which we refer to as “snaps." We are currently exploring models of how these centromere-like snaps are generated and what role they play in faithful chromosome replication, repair and segregation.
DNA Replication: In vitro, precatenanes form along DNA segments that are under positive helical tension (overwound). The presence of precatenanes behind replication forks in vivo implies that replicative helicases generate tension that outpaces the relaxing ability of topoisomerases (forks can travel at an astounding 1000 bp/sec!). Theoretically, this tension rapidly spins the replication fork causing the two replicated DNAs to wrap around each other. Our lab is investigating whether DNA-bound proteins act as topological barriers during replication, driving the formation of precatenanes. The basic enzymology of DNA replication is well conserved among all life, and it has recently been shown that eukaryotic chromosomes are also highly catenated along their lengths.
We expect that our work will lead to a better understanding of the factors that limit replication fork speed, cause replication fork stalling (quickly leading to double-strand breaks), and inhibit chromosome segregation. These events in humans are a major source of genomic instability and diseases including cancer.
Selected Publications
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Visser BJ, Joshi MC, Bates D. " Multi-locus imaging of the E. coli chromosome by Fluorescent In Situ Hybridization. " Methods Mol Biol. 2017 ; 1624 : 213-226.
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Bates D, Pettitt BM, Buck GR, Zechiedrich L. " Importance of entanglement and disentanglement during DNA replication and segregation. " Phys Life. 2016 ; 18 : 160-4.
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Xia J, Chen L, Mei Q, Ma CH, Halliday JA, Lin HY, Magnan D, Pribis JP, Fitzgerald DM, Hamilton HM, Richters M, Nehring R, Shen X, Li L, Bates D, Hastings PJ, Herman C, Jayaram M, Rosenberg SM. " Holliday-junction trap shows how cells use recombination and a junction-guardian role of RecQ
helicase. " Sci Adv.. 2016 ; 2 : e1601605.
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Moore JM, Magnan D, Mojica AK, Núñez MA, Bates D, Rosenberg SM, Hastings PJ. " " Genetics. 2015 Oct 23; 115 (178970)
Pubmed PMID: .
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