About

Nancy Kleckner is the Herchel Smith Professor of Molecular Biology at Harvard University. She is a faculty member in the Department of Molecular & Cellular Biology. Her research focuses on molecular biology, with a particular emphasis on understanding the mechanisms underlying biological processes at the molecular level. As a prominent figure in her field, she contributes to advancing knowledge in molecular biology through her research and teaching activities.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Computer Science
• Chemistry
• Computational biology
• Microbiology
• Cell biology

Selected publications

• Faulted ZnS:Mn,Cu Nanorods Provide Nanoscale Mechanoluminescence Excitation in a Biologically Relevant Force Range

  ACS Nano · 2026-03-12

  articleOpen accessSenior author

  Mechanoluminescent materials emit photons when subjected to mechanical stress, with the emission intensity proportional to the applied force. This property enables their use as force sensors with a direct optical readout. However, spatial resolution of the force sensing is limited by the crystal size, with thresholds near 100 μm. Seeking to overcome this limitation, we introduce stacking fault-rich, highly crystalline, monodisperse ZnS nanorods codoped with Mn and Cu (ZnS:Mn,Cu) approximately 60 × 20 nm in size. The design of these nanorods leveraged insights from the nanoscale mechanism for elastic mechanoluminescence at stacking faults that was known for micrometer-scale ZnS crystals doped with Mn. Here, ensemble impact tests confirm that the faulted ZnS:Mn,Cu nanorods indeed exhibit mechanoluminescence, where the intensity is dependent on the concentrations of both Mn and Cu. The mechanoluminescence intensity peaks at 0.15 wt % of Mn. Furthermore, a proportional increase in intensity is observed within the range of the tested Cu concentrations. The mechanoluminescence of individual nanorods with optimized dopant concentrations was investigated by using correlated atomic force and optical microscopy, with multiple force cycles delivered to individual nanorods to track force-dependent changes in the intensity of the optical emission on a single-particle level. Mechanoluminescence was detected at force amplitudes ranging between 13.9 and 100 nN, with no observable change in the nanorod morphology. Our results confirm that the introduction of stacking faults enables excitation of repeatable elastic mechanoluminescence in single nanometer crystals, which are not embedded in any matrix. This approach enables high-resolution force sensing in three dimensions in the low-nanometer range relevant to biological applications.

  PublisherOA PDFDOI

• Future Directions of the Prokaryotic Chromosome Field

  Molecular Microbiology · 2025-02-01 · 3 citations

  reviewOpen access

  In September 2023, the Biology and Physics of Prokaryotic Chromosomes meeting ran at the Lorentz Center in Leiden, The Netherlands. As part of the workshop, those in attendance developed a series of discussion points centered around current challenges for the field, how these might be addressed, and how the field is likely to develop over the next 10 years. The Lorentz Center staff facilitated these discussions via tools aimed at optimizing productive interactions. This Perspective article is a summary of these discussions and reflects the state-of-the-art of the field. It is expected to be of help to colleagues in advancing their own research related to prokaryotic chromosomes and inspiring novel interdisciplinary collaborations. This forward-looking perspective highlights the open questions driving current research and builds on the impressive recent progress in these areas as represented by the accompanying reviews, perspectives, and research articles in this issue. These articles underline the multi-disciplinary nature of the field, the multiple length scales at which chromatin is studied in vitro and in and highlight the differences and similarities of bacterial and archaeal chromatin and chromatin-associated processes.

  PublisherOA PDFDOI

• Crossover interference mediates multiscale patterning along meiotic chromosomes

  Nature Communications · 2025-11-25 · 3 citations

  articleOpen accessSenior author

  Meiotic crossover interference is a one-dimensional spatial patterning process that produces evenly-spaced crossovers. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process sets up two interdigitated patterns, of shorter and longer periodicity, by "two-tiered" patterning. Both tiers comprise clustered assemblies of three types of molecules ("triads") representing the three major components of meiotic chromosomes (crossover recombination, axes, and the synaptonemal complex). One tier of triads occurs at sites of majority ("canonical") crossovers. Second tier triads are more widely spaced but also exhibit interference, dependent on the same functions as canonical crossover interference. Diverse lines of evidence suggest that second tier triads arise at sites of previously mysterious "minority" crossovers. Finally, conserved protein remodeler Pch2/TRIP13 modulates the abundance of triad components, specifically in longer periodicity triads, dynamically in real time. Potential roles of triad structure, mechanisms of two-tiered patterning, and the nature of minority crossovers are discussed.

  PublisherOA PDFDOI

• Meiosis through three centuries

  Chromosoma · 2024-04-01 · 13 citations

  reviewOpen accessCorresponding

  Meiosis is the specialized cellular program that underlies gamete formation for sexual reproduction. It is therefore not only interesting but also a fundamentally important subject for investigation. An especially attractive feature of this program is that many of the processes of special interest involve organized chromosomes, thus providing the possibility to see chromosomes "in action". Analysis of meiosis has also proven to be useful in discovering and understanding processes that are universal to all chromosomal programs. Here we provide an overview of the different historical moments when the gap between observation and understanding of mechanisms and/or roles for the new discovered molecules was bridged. This review reflects also the synergy of thinking and discussion among our three laboratories during the past several decades.

  PublisherOA PDFDOI

• Rapid Homolog Juxtaposition During Meiotic Chromosome Pairing

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-27 · 1 citations

  preprintOpen accessSenior authorCorresponding

  A central basic feature of meiosis is pairing of homologous maternal and paternal chromosomes ("homologs") intimately along their lengths. Recognition between homologs and their juxtaposition in space are mediated by axis-associated DNA recombination complexes. Additional effects ensure that pairing occurs without ultimately giving entanglements among unrelated chromosomes. Here we examine the process of homolog juxtaposition in real time by 4D fluorescence imaging of tagged chromosomal loci at high spatio-temporal resolution in budding yeast. We discover that corresponding loci start coming together from a quite large distance (∼1.8 µm) and progress to completion of pairing in a very short time, usually less than six minutes (thus, "rapid homolog juxtaposition" or "RHJ"). Juxtaposition initiates by motion-mediated extension of a nascent interhomolog DNA linkage, raising the possibility of a tension-mediated trigger. In a first transition, homolog loci move rapidly together (in ∼30 sec, at speeds of up to ∼60 nm/sec) into a discrete intermediate state corresponding to canonical ∼400 nm axis distance coalignment. Then, after a short pause, crossover/noncrossover differentiation (crossover interference) mediates a second short, rapid transition that brings homologs even closer together. If synaptonemal complex (SC) component Zip1 is present, this transition concomitantly gives final close pairing by axis juxtaposition at ∼100 nm, the "SC distance". We also find that: (i) RHJ occurs after chromosomes acquire their prophase chromosome organization; (ii) is nearly synchronously over thirds (or more) of chromosome lengths; but (iii) is asynchronous throughout the genome. Furthermore, cytoskeleton-mediated movement is important for the timing and distance of RHJ onset and also for ensuring normal progression. Potential implications for local and global aspects of pairing are discussed.

  PublisherOA PDFDOI

• Canonical and noncanonical roles of Hop1 are crucial for meiotic prophase in the fungus Sordaria macrospora

  PLoS Biology · 2024-07-01 · 3 citations

  articleOpen accessCorresponding

  We show here that in the fungus Sordaria macrospora, the meiosis-specific HORMA-domain protein Hop1 is not essential for the basic early events of chromosome axis development, recombination initiation, or recombination-mediated homolog coalignment/pairing. In striking contrast, Hop1 plays a critical role at the leptotene/zygotene transition which is defined by transition from pairing to synaptonemal complex (SC) formation. During this transition, Hop1 is required for maintenance of normal axis structure, formation of SC from telomere to telomere, and development of recombination foci. These hop1Δ mutant defects are DSB dependent and require Sme4/Zip1-mediated progression of the interhomolog interaction program, potentially via a pre-SC role. The same phenotype occurs not only in hop1Δ but also in absence of the cohesin Rec8 and in spo76-1, a non-null mutant of cohesin-associated Spo76/Pds5. Thus, Hop1 and cohesins collaborate at this crucial step of meiotic prophase. In addition, analysis of 4 non-null mutants that lack this transition defect reveals that Hop1 also plays important roles in modulation of axis length, homolog-axis juxtaposition, interlock resolution, and spreading of the crossover interference signal. Finally, unexpected variations in crossover density point to the existence of effects that both enhance and limit crossover formation. Links to previously described roles of the protein in other organisms are discussed.

  PublisherOA PDFDOI

• Crossover Interference Mediates Multiscale Patterning Along Meiotic Chromosomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-31 · 5 citations

  preprintOpen accessSenior authorCorresponding

  The classical phenomenon of crossover interference is a one-dimensional spatial patterning process that produces evenly spaced crossovers during meiosis. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process also sets up a second, interdigitated pattern of related but longer periodicity, in a "two-tiered" patterning process. The second tier corresponds to a previously mysterious minority set of crossovers. Thus, in toto, the two tiers account for all detected crossover events. Both tiers of patterning set up spatially clustered assemblies of three types of molecules ("triads") representing the three major components of meiotic chromosomes (crossover recombination complexes and chromosome axis and synaptonemal complex components), and give focal and domainal signals, respectively. Roles are suggested. All observed effects are economically and synthetically explained if crossover patterning is mediated by mechanical forces along prophase chromosomes. Intensity levels of domainal triad components are further modulated, dynamically, by the conserved protein remodeler Pch2/TRIP13.

  PublisherOA PDFDOI

• Rapid homologue juxtaposition during meiotic chromosome pairing

  Nature · 2024-10-02 · 6 citations

  articleSenior author
  PublisherDOI

• RPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination

  Nucleic Acids Research · 2024-02-10 · 9 citations

  articleOpen access

  Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.

  PublisherOA PDFDOI

• Dynamic Arrangements of Replication Protein A-Single Stranded DNA in Meiotic Double-Strand Break Repair

  SSRN Electronic Journal · 2023-01-01

  preprintOpen access
  PublisherDOI

Recent grants

• Physical Studies of the Translocatable Genetic Elements in Bacteria

  NSF · $353k · 1989–1993

• NIH Grant R01GM044794

  NIH · $16.8M · 2020

• Chromosome organization and function in time and space: meiosis, mitosis and E. coli

  NIH · $6.2M · 2020–2030

• NIH Grant R01GM025326

  NIH · $13.9M · 2020

• NIH Grant R37GM025326

  NIH · $5.0M · 2001

Frequent coauthors

• Denise Zickler

  CEA Paris-Saclay

  80 shared

• Ruth Padmore

  University of Ottawa

  29 shared

• Job Dekker

  Short and Associates (United States)

  26 shared

• Gareth H. Jones

  25 shared

• Jim Henle

  Université Paris-Sud

  25 shared

• An Embo

  Vlaams Instituut voor Biotechnologie

  25 shared

• Mike May

  25 shared

• Rachel M. Chalmers

  Public Health Wales

  25 shared

Labs

• Nancy KlecknerPI

Education

• B.S., Molecular and Cell Biology

  University of California, Berkeley

  1981

• Ph.D., Molecular and Cell Biology

  University of California, Berkeley

  1986

Awards & honors

• Thomas Hunt Morgan Lifetime Achievement Award, 2016