Sue Jinks-Robertson

Overview:

My research focuses on the regulation of genetic stability and primarily uses budding yeast (Saccharomyces cerevisiae) as a model genetic system.  The two primary research goals in the budding yeast system are (1) defining molecular structures and mechanisms of mitotic recombination intermediates and (2) understanding how and why transcription destabilizes the underlying DNA template.  We also have initiated studies of mutagenesis in the pathogenic fungus Cryptococcus neoformans.  We have found that a shift to the human body temperature mobilizes transposable elements, and suggest that this promotes rapid adaptation to the harsh host environment.  

Positions:

Professor of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Vice-Chair in the Department of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1983

University of Wisconsin at Madison

Grants:

Regulation of mitotic genome stability in yeast.

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

What Happens at a Double Strand Break: Investigating the Role of DNA End Structure in Homologous Recombination

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Investigating the origin of spontaneous mitotic homologous recombination in Saccharomyces cerevisiae

Administered By
Molecular Genetics and Microbiology
Awarded By
American Heart Association
Role
Principal Investigator
Start Date
End Date

Regulation of mitotic genome stability in yeast

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Topoisomerase 1 and mutagenesis in yeast

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae.

High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2DeltaBgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2DeltaBgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.
Authors
Morey, NJ; Greene, CN; Jinks-Robertson, S
MLA Citation
Morey, N. J., et al. “Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae..” Genetics, vol. 154, no. 1, Jan. 2000, pp. 109–20.
URI
https://scholars.duke.edu/individual/pub796028
PMID
10628973
Source
pubmed
Published In
Genetics
Volume
154
Published Date
Start Page
109
End Page
120

Time-dependent mitotic recombination in Saccharomyces cerevisiae.

The time-dependent appearance of prototrophic recombinants between heterologously located artificial repeats has been studied in Saccharomyces cerevisiae. While initial prototrophic colony numbers from independent cultures were highly variable, additional recombinants were found to arise daily at roughly constant rates irrespective of culture. These late-appearing recombinants could be accounted for neither by detectable growth on the selective media nor by delayed appearance of recombinants present at the time of selective plating. Significantly, at no time did the distributions of recombinants fully match those expected according to the Luria-Delbruck model and, in fact, after the first day, the distributions much more closely approximated a Poisson distribution. Prototrophic recombinants accumulated not only on the relevant selective medium, but also on media unrelated to the acquired prototrophy.
Authors
Steele, DF; Jinks-Robertson, S
MLA Citation
Steele, D. F., and S. Jinks-Robertson. “Time-dependent mitotic recombination in Saccharomyces cerevisiae..” Curr Genet, vol. 23, no. 5–6, May 1993, pp. 423–29. Pubmed, doi:10.1007/bf00312629.
URI
https://scholars.duke.edu/individual/pub796042
PMID
8319298
Source
pubmed
Published In
Current Genetics
Volume
23
Published Date
Start Page
423
End Page
429
DOI
10.1007/bf00312629

Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo.

Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events are dependent on DNA topoisomerase I (Top1) and are initiated by Top1 incision at the relevant ribonucleotide 3'-phosphodiester. A requirement for the re-ligation activity of Top1 led us to propose a sequential cleavage model for Top1-dependent mutagenesis at ribonucleotides. Here, we test key features of this model via parallel in vitro and in vivo analyses. We find that the distance between two Top1 cleavage sites determines the deletion size and that this distance is inversely related to the deletion frequency. Following the creation of a gap by two Top1 cleavage events, the tandem repeat provides complementarity that promotes realignment to a nick and subsequent Top1-mediated ligation. Complementarity downstream of the gap promotes deletion formation more effectively than does complementarity upstream of the gap, consistent with constraints to realignment of the strand to which Top1 is covalently bound. Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process.
Authors
Cho, J-E; Huang, S-YN; Burgers, PM; Shuman, S; Pommier, Y; Jinks-Robertson, S
MLA Citation
Cho, Jang-Eun, et al. “Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo..” Nucleic Acids Res, vol. 44, no. 16, Sept. 2016, pp. 7714–21. Pubmed, doi:10.1093/nar/gkw495.
URI
https://scholars.duke.edu/individual/pub1147487
PMID
27257064
Source
pubmed
Published In
Nucleic Acids Res
Volume
44
Published Date
Start Page
7714
End Page
7721
DOI
10.1093/nar/gkw495

The mechanism of nucleotide excision repair-mediated UV-induced mutagenesis in nonproliferating cells.

Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such two-strand mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colony-color system was used to examine the genetic control of UV-induced mutagenesis in nondividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production of these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32, and Rad5) and in the early steps of the DNA-damage checkpoint response (Rad17, Mec3, Ddc1, Mec1, and Rad9) were required for the production of two-strand mutations. There was no involvement, however, for the Pol η translesion synthesis DNA polymerase, the Mms2-Ubc13 postreplication repair complex, downstream DNA-damage checkpoint factors (Rad53, Chk1, and Dun1), or the Exo1 exonuclease. Our data support models in which UV-induced mutagenesis in nondividing cells occurs during the Pol ζ-dependent filling of lesion-containing, NER-generated gaps. The requirement for specific DNA-damage checkpoint proteins suggests roles in recruiting and/or activating factors required to fill such gaps.
Authors
Kozmin, SG; Jinks-Robertson, S
MLA Citation
Kozmin, Stanislav G., and Sue Jinks-Robertson. “The mechanism of nucleotide excision repair-mediated UV-induced mutagenesis in nonproliferating cells..” Genetics, vol. 193, no. 3, Mar. 2013, pp. 803–17. Pubmed, doi:10.1534/genetics.112.147421.
URI
https://scholars.duke.edu/individual/pub952315
PMID
23307894
Source
pubmed
Published In
Genetics
Volume
193
Published Date
Start Page
803
End Page
817
DOI
10.1534/genetics.112.147421

Sequence divergence impedes crossover more than noncrossover events during mitotic gap repair in yeast.

Homologous recombination between dispersed repeated sequences is important in shaping eukaryotic genome structure, and such ectopic interactions are affected by repeat size and sequence identity. A transformation-based, gap-repair assay was used to examine the effect of 2% sequence divergence on the efficiency of mitotic double-strand break repair templated by chromosomal sequences in yeast. Because the repaired plasmid could either remain autonomous or integrate into the genome, the effect of sequence divergence on the crossover-noncrossover (CO-NCO) outcome was also examined. Finally, proteins important for regulating the CO-NCO outcome and for enforcing identity requirements during recombination were examined by transforming appropriate mutant strains. Results demonstrate that the basic CO-NCO outcome is regulated by the Rad1-Rad10 endonuclease and the Sgs1 and Srs2 helicases, that sequence divergence impedes CO to a much greater extent than NCO events, that an intact mismatch repair system is required for the discriminating identical and nonidentical repair templates, and that the Sgs1 and Srs2 helicases play additional, antirecombination roles when the interacting sequences are not identical.
Authors
Welz-Voegele, C; Jinks-Robertson, S
MLA Citation
Welz-Voegele, Caroline, and Sue Jinks-Robertson. “Sequence divergence impedes crossover more than noncrossover events during mitotic gap repair in yeast..” Genetics, vol. 179, no. 3, July 2008, pp. 1251–62. Pubmed, doi:10.1534/genetics.108.090233.
URI
https://scholars.duke.edu/individual/pub795999
PMID
18562664
Source
pubmed
Published In
Genetics
Volume
179
Published Date
Start Page
1251
End Page
1262
DOI
10.1534/genetics.108.090233

Research Areas:

DNA Repair
Gene Conversion
Genetic recombination
Insertional mutagenesis
Mutagenesis
Recombinational DNA Repair
Transcription