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Diana Libuda

Diana Libuda

Assistant professor, Biology
Member, IMB

Ph.D., Harvard University
B.Sc., University of California, Los Angeles

Lab website
Office: Streisinger 375A
Lab: Streisinger 375, 381, 396

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Research Interests

The Libuda Lab investigates how developing sperm and eggs repair DNA breaks with the proper chromosome template to ensure faithful genome inheritance from one generation to another.

Double strand DNA breaks (DSBs), potentially catastrophic events, occur during both mitosis and meiosis and must be repaired to maintain genomic stability. The inaccurate repair of DSBs contributes to the development and progression of cancer. During meiosis, DSBs are intentionally induced, and their formation and repair occur under precise regulation both to restore genome integrity prior to cell division and to promote proper chromosome segregation. Meiotic errors in chromosome segregation contribute to miscarriages, stillbirths, and birth defects. While repair of DSBs with the appropriate chromosome template (homolog) is necessary for genomic integrity, very little is known as to how germ cells achieve this repair template preference in the presence of other potential templates with nearly identical sequences (sister chromatids; Figure 1).


To understand how chromosomes are able to access distinct repair templates and pathways depending on chromosomal and cellular context, the Libuda Lab combines genetic, cytological, molecular, and biochemical methods in the Caenorhabditis elegans model system. The C. elegans system is advantageous for investigating how DSB repair decisions are imposed and regulated during meiosis, in part because the events of meiotic prophase are organized in a spatial-temporal gradient along the distal-proximal axis of the gonad, enabling visualization of all the stages of meiosis in a single gonad (Figure 2). Utilizing high-resolution and super-resolution microscopy, the germ line allows imaging of DNA repair events along chromosome structures of intact germ cells where the three-dimensional nuclear architecture is preserved (Figure 3).

figure figure

Some of our current interests include:

Temporal features of DNA repair template choice

We have developed a set of assays that: 1) induce formation of a DSB at a defined site; and, 2) detect and distinguish DSB repair outcomes with either the homolog and sister chromatid template at specific stages of meiotic prophase. Utilizing these assays, we are testing for a hypothesized switch in partner choice during meiotic prophase progression. Further, we are identifying chromosome-structural features and bound proteins that influence partner choice.

Molecular mechanisms of DNA repair template choice

Utilizing a variety of genetic and cytological assays, we are investigating how specific chromosome structures, checkpoint kinases, and repair pathways affect the partner choice decision. In addition, we are performing genetic screens to identify additional factors involved in the DNA repair partner choice decision.


Dynamics of DSB repair

Utilizing live imaging of ongoing DSB repair events in whole, intact worms, we are revealing how duration and dynamic localization of early DSB repair stages influence and ensure DSBs are repaired in the appropriate context (Figure 5).


Male germline-specific responses to temperature

Our lab has identified a temperature condition that induces a phenotype only found in male germlines. We are investigating this phenotype to understand how chromosomes in male germlines differ in their response to changes in temperature.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

DNA helicase HIM-6/BLM both promotes MutSĪ³-dependent crossovers and antagonizes MutSĪ³-independent interhomolog associations during caenorhabditis elegans meiosis.
Schvarzstein M, Pattabiraman D, Libuda DE, Ramadugu A, Tam A, Martinez-Perez E, Roelens B, Zawadzki KA, Yokoo R, Rosu S, Severson AF, Meyer BJ, Nabeshima K, Villeneuve AM
Genetics 2014 Sep;198(1):193-207
The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance.
Rosu S, Zawadzki KA, Stamper EL, Libuda DE, Reese AL, Dernburg AF, Villeneuve AM
PLoS Genet 2013;9(8):e1003674
Meiotic chromosome structures constrain and respond to designation of crossover sites.
Libuda DE, Uzawa S, Meyer BJ, Villeneuve AM
Nature 2013 Oct 31;502(7473):703-6
Robust crossover assurance and regulated interhomolog access maintain meiotic crossover number.
Rosu S, Libuda DE, Villeneuve AM
Science 2011 Dec 2;334(6060):1286-9
Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development.
Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM
Development 2003 Jun;130(12):2779-91