About

Karen Oegema is a Professor of Cell and Developmental Biology at UCSD, working within the Department of Cellular and Molecular Medicine. Her research employs parallel approaches in mammalian cells and the C. elegans embryo as a metazoan model system to study cell division and embryonic development. Her lab focuses on understanding the mechanisms of cell division, cell cycle control, genetics and genomics, signal transduction, stem cell biology, and systems biology. Her work has contributed to elucidating processes such as centrosome remodeling during mitosis, kinetochore-microtubule attachments, centriole assembly, and the regulation of mitotic fidelity, among other topics in cell biology.

Research topics

• Cell biology
• Biology
• Chemistry
• Physics
• Genetics
• Biochemistry

Selected publications

• Inhibitor-2 directs formation of PP1 holoenzymes through a docking motif-dependent transfer of catalytic subunits to adapters

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-17

  articleOpen access

  The catalytic subunits of protein phosphatase 1 (PP1) achieve spatiotemporal substrate specificity by assembling with diverse regulatory adapters to form holoenzymes. Three conserved proteins-Sds22, Inhibitor-2 and Inhibitor-3-facilitate loading of PP1 catalytic subunits (PP1cs) onto adapters. We show here that Inhibitor-2 is central to a dynamic cycle that directs formation of adapter-bound PP1 holoenzymes. Inhibitor-2 engages PP1cs via two adapter-like docking motifs (RVxF and SILK) and an active site-binding inhibitory region. While Inhibitor-2 depletion produced moderate phenotypes, mutation of its RVxF docking motif caused severe defects resembling global PP1c inhibition. The RVxF mutant did not prevent PP1c binding or reduce PP1c stability but inhibited formation of adapter-bound holoenzymes. The severe effects of the RVxF mutation were suppressed by linked mutation of the inhibitory active site-binding motif. These results suggest that Inhibitor-2 is integral to a dynamic cycle that delivers PP1cs to adapters, with its RVxF motif being critical for coupling relief of active site inhibition to adapter handoff.

  PublisherOA PDFDOI

• TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization

  Nature Structural & Molecular Biology · 2025-05-25 · 3 citations

  articleSenior author
  PublisherDOI

• The mitotic stopwatch synergizes with mild p53 activation to halt cell proliferation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-03

  articleOpen accessSenior authorCorresponding

  ABSTRACT The mitotic stopwatch suppresses proliferation of cell lineages experiencing prolonged mitosis that are prone to chromosome missegregation and tumorigenesis. It converts extended mitotic duration into heritable USP28–53BP1 complexes that stabilize p53 and accumulate over generations. To identify genes whose knockout activates the stopwatch, we performed a CRISPR/Cas9 screen comparing dropout kinetics of essential-gene gRNAs in cells lacking versus possessing the stopwatch. Two classes of knockouts emerged: one (27/60 top hits) that prolonged mitosis, and another (33/60 top hits) that mildly elevated p53 without significant mitotic defects, indicating that the stopwatch synergizes with mild p53 activation to halt proliferation. Mild p53 elevation lowered the stopwatch complex threshold for daughter cell arrest and slightly prolonged mitosis. Integrated over successive divisions, the cumulative effect of multiple short mitotic extensions triggered stopwatch-dependent arrest. Thus, the mitotic stopwatch endows the p53 network with a durable lineage memory of modest stress, explaining its tumor-suppressive role.

  PublisherDOI

• A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-01

  preprintOpen access

  Abstract Accurate chromosome segregation requires dynamic kinetochore–microtubule attachments that, under the regulation of Aurora family kinases, biorient and align replicated chromosomes. In C. elegans , Aurora A acts with the TPX2-related activator TPXL-1 to regulate these attachments and control spindle length. We show that, in addition to prominent spindle pole localization, TPXL-1–AurA has a chromatin-associated pool positioned between the sister kinetochores. Structural modeling and biochemical analysis support TPXL-1 directly recognizing the nucleosome acidic patch via an arginine anchor. Disrupting this interaction selectively removed chromatin-bound TPXL-1–AurA and caused chromosome missegregation, whereas elevation of the chromatin pool disrupted chromosome alignment. These opposing perturbations inversely affected kinetochore recruitment of the microtubule-binding Ska complex. These results support spatially distinct TPXL-1–AurA populations acting sequentially, with the spindle pole pool controlling spindle length by switching kinetochores out of a depolymerization-coupled state, and the chromatin pool controlling attachment stabilization to ensure biorientation prior to anaphase.

  PublisherOA PDFDOI

• Phosphorylation remodels the mitotic centrosome matrix to generate bipartite γ-tubulin complex docking sites

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-21

  preprintOpen accessSenior authorCorresponding

  Abstract Mitotic centrosomes consist of centrioles surrounded by a proteinaceous matrix that docks and activates γ-tubulin complexes (γTuCs) to nucleate microtubules for spindle assembly. During mitotic entry, phosphorylation at centrosomes remodels CDK5RAP2 family matrix proteins to generate γTuC docking sites. We address the mechanism of this conversion using C. elegans SPD-5 as a model. We show that SPD-5 contains two regions, PRGB1 and PRGB2, that are each sufficient for Polo-Like Kinase 1 (PLK1) phosphorylation–regulated γTuC binding. We define key phosphosites in each region and uncover autoinhibition mediated by interactions within and between them. PRGB2 is dimeric and requires γTuCs containing the Mozart family microprotein MZT-1 for binding, whereas PRGB1 is monomeric and binds independently of MZT-1. Our results support PLK1 phosphorylation inducing a conformational change that enables MZT-1–dependent PRGB2 binding, which in turn relieves PRGB1 inhibition. Such a multi-step mechanism would ensure robust spindle assembly by restricting microtubule nucleation in space and time.

  PublisherOA PDFDOI

• Hybrid incompatibility emerges at the one-cell stage in interspecies Caenorhabditis embryos

  Current Biology · 2025-07-01 · 1 citations

  article
  PublisherDOI

• TRIM37 employs peptide motif recognition and substrate-dependent oligomerization to prevent ectopic spindle pole assembly

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-10 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Tightly controlled duplication of centrosomes, the major microtubule-organizing centers of animal cells, ensures bipolarity of the mitotic spindle and accurate chromosome segregation. The RBCC (RING-B-box-coiled coil) ubiquitin ligase TRIM37, whose loss is associated with elevated chromosome missegregation and the tumor-prone developmental human disorder Mulibrey nanism, prevents the formation of ectopic spindle poles that assemble around structured condensates containing the centrosomal protein centrobin. Here, we show that TRIM37's TRAF domain, unique in the extended TRIM family, engages peptide motifs in centrobin to suppress condensate formation. TRIM proteins form anti-parallel coiled-coil dimers with RING-B-box domains on each end. Oligomerization due to RING-RING interactions and conformational regulation by B-box-2-B-box-2 interfaces are critical for TRIM37 to suppress centrobin condensate formation. These results indicate that, analogous to anti-viral TRIM ligases, TRIM37 activation is linked to the detection of oligomerized substrates. Thus, TRIM37 couples peptide motif recognition and substrate-dependent oligomerization to effect ubiquitination-mediated clearance of ectopic centrosomal protein assemblies.

  PublisherOA PDFDOI

• Phospho-KNL-1 recognition by a TPR domain targets the BUB-1–BUB-3 complex to <i>C. elegans</i> kinetochores

  The Journal of Cell Biology · 2024-04-05 · 1 citations

  articleOpen access

  During mitosis, the Bub1-Bub3 complex concentrates at kinetochores, the microtubule-coupling interfaces on chromosomes, where it contributes to spindle checkpoint activation, kinetochore-spindle microtubule interactions, and protection of centromeric cohesion. Bub1 has a conserved N-terminal tetratricopeptide repeat (TPR) domain followed by a binding motif for its conserved interactor Bub3. The current model for Bub1-Bub3 localization to kinetochores is that Bub3, along with its bound motif from Bub1, recognizes phosphorylated "MELT" motifs in the kinetochore scaffold protein Knl1. Motivated by the greater phenotypic severity of BUB-1 versus BUB-3 loss in C. elegans, we show that the BUB-1 TPR domain directly recognizes a distinct class of phosphorylated motifs in KNL-1 and that this interaction is essential for BUB-1-BUB-3 localization and function. BUB-3 recognition of phospho-MELT motifs additively contributes to drive super-stoichiometric accumulation of BUB-1-BUB-3 on its KNL-1 scaffold during mitotic entry. Bub1's TPR domain interacts with Knl1 in other species, suggesting that collaboration of TPR-dependent and Bub3-dependent interfaces in Bub1-Bub3 localization and functions may be conserved.

  PublisherOA PDFDOI

• Automated profiling of gene function during embryonic development

  Cell · 2024-05-16 · 12 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• The kinase ZYG-1 phosphorylates the cartwheel protein SAS-5 to drive centriole assembly in C. elegans

  EMBO Reports · 2024-05-14 · 4 citations

  articleOpen access

  Abstract Centrioles organize centrosomes, the cell’s primary microtubule-organizing centers (MTOCs). Centrioles double in number each cell cycle, and mis-regulation of this process is linked to diseases such as cancer and microcephaly. In C. elegans , centriole assembly is controlled by the Plk4 related-kinase ZYG-1, which recruits the SAS-5–SAS-6 complex. While the kinase activity of ZYG-1 is required for centriole assembly, how it functions has not been established. Here we report that ZYG-1 physically interacts with and phosphorylates SAS-5 on 17 conserved serine and threonine residues in vitro. Mutational scanning reveals that serine 10 and serines 331/338/340 are indispensable for proper centriole assembly. Embryos expressing SAS-5 S10A exhibit centriole assembly failure, while those expressing SAS-5 S331/338/340A possess extra centrioles. We show that in the absence of serine 10 phosphorylation, the SAS-5–SAS-6 complex is recruited to centrioles, but is not stably incorporated, possibly due to a failure to coordinately recruit the microtubule-binding protein SAS-4. Our work defines the critical role of phosphorylation during centriole assembly and reveals that ZYG-1 might play a role in preventing the formation of excess centrioles.

  PublisherOA PDFDOI

Recent grants

• Analysis of Centrosome Dynamics

  NIH · $6.6M · 2006–2026

• INNER CENTROMERE TARGETING OF THE CHROMOSOME PASSENGER COMPLEX

  NIH · $10.6M · 2011–2016

Frequent coauthors

• Arshad Desai

  Ludwig Cancer Research

  318 shared

• Shaohe Wang

  Howard Hughes Medical Institute

  70 shared

• Pablo Lara-González

  61 shared

• Rebecca A. Green

  Bristol-Myers Squibb (United States)

  58 shared

• Anthony A. Hyman

  Max Planck Institute of Molecular Cell Biology and Genetics

  49 shared

• Dhanya K. Cheerambathur

  Wellcome Centre for Cell Biology

  47 shared

• Renat N. Khaliullin

  Ludwig Cancer Research

  38 shared

• Paul S. Maddox

  University of North Carolina at Chapel Hill

  37 shared

Education

• Ph.D.

  University of California San Francisco

  1996

• B.S.

  California Institute of Technology

  1989