About

Kevin Corbett is a Professor of Cellular and Molecular Medicine at UC San Diego. His laboratory focuses on the molecular mechanisms of chromosome segregation in meiosis, utilizing biochemistry, X-ray crystallography, and genetics in Saccharomyces cerevisiae to investigate the structure, function, and interactions of proteins involved in meiotic chromosome pairing, crossover initiation and maturation, and chromosome segregation. A recent research focus involves studying the structure and function of bacterial HORMA domain proteins, a family of signaling proteins previously thought to exist only in eukaryotes. His research activities include exploring the molecular mechanisms of chromosome organization and recombination control, as well as the signaling pathways involving bacterial HORMA and Pch2-like proteins. Corbett's work has contributed to understanding the architecture of meiotic chromosomes, the role of cohesin complexes, and the broader implications of chromosome behavior in cell division. His research has been supported by multiple NIH grants, and he has authored numerous publications in the field of molecular biology and genetics.

Research topics

• Biology
• Cell biology
• Biochemistry
• Chemistry
• Virology
• Genetics
• Internal medicine
• Physics
• Materials science
• Medicine
• Molecular biology
• Biophysics
• Computational biology

Selected publications

• Structure of the <i>Chimalliviridae</i> bacteriophage Goslar reveals host recognition and infection machinery

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-22

  articleSenior author

  SUMMARY Large-genome bacteriophages (phages) of the Chimalliviridae family possess a distinctive life cycle, building compartments inside infected bacterial cells that broadly protect their genomes from host defenses. Here, we use cryoelectron microscopy to determine a high-resolution structure of the E. coli -infecting Chimalliviridae phage Goslar, generating a composite model with 2,888 protein chains from 28 different structural proteins, totaling over 1.4 million amino acid residues. Our structure reveals the architecture of the Goslar capsid, portal, tail, and baseplate, highlighting structural similarities and differences with other tailed phages. Combining our structural data with quantitative mass spectrometry of Goslar virions, we identify several high-copy virion-associated proteins that likely play key roles when injected into host cells upon infection. We also identify a Chimalliviridae -specific family of proteins that form long, flexible filaments anchored at the phage baseplate and which incorporate carbohydrate-binding domains, suggesting a key role in host recognition.

  PublisherDOI

• A DNA damage-activated kinase controls bacterial immune pathway expression

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-03

  articleOpen accessSenior authorCorresponding

  Bacteria encode myriad stress-response pathways that protect their hosts against both internal and external threats. A key question is how these pathways are regulated, especially anti-phage immune pathways that mediate host cell killing. Here, we identify two proteins termed CapK and CapS that are encoded upstream of diverse immune operons, and regulate their expression in response to DNA damage. CapK resembles bacterial anti-sigma factor kinases, and CapS resembles these proteins' STAS domain antagonists. CapS is a DNA-binding transcriptional repressor, and phosphorylation of CapS by CapK results in dissociation of a CapS homodimer and de-repression of transcription. CapK's kinase activity is directly activated by single-stranded DNA generated as a by-product of DNA repair. Finally, we show that CapK and CapS-like proteins have been co-opted into an anti-phage toxin-antitoxin system with a VapC-like protein, where they similarly respond to DNA damage to activate VapC's nuclease activity. Overall, our results reveal how a kinase-substrate pair can regulate expression of an adjacent operon in response to DNA damage, and highlight the modularity of immune and other stress-response pathways.

  PublisherDOI

• Mechanism and reconstitution of circadian transcription in cyanobacteria

  Nature Structural & Molecular Biology · 2026-02-01

  articleOpen access

  Circadian biological clocks evolved across kingdoms of life as an adaptation to predictable cycles of sunrise and sunset. In the cyanobacterium Synechococcus elongatus, a protein-based clock precisely controls when different genes are turned on and off during the 24-h day but the phasing mechanism remains unclear. Here we show the molecular basis of this regulation and reconstitute clock-controlled transcription in vitro using purified components. Biochemical and structural analyses revealed that the clock-regulated transcription factor RpaA can function as either an activator or a repressor of cyanobacterial RNA polymerase, depending on its binding position relative to core promoter elements. Leveraging the repressor mechanism, we developed a heterologous in vitro system driven by bacteriophage T7 RNA polymerase that sustains circadian transcription for multiple days. These findings explain how a single clock output generates opposite phases of gene expression and define the minimal components for circadian clock function, enabling synthetic or biotechnological applications.

  PublisherDOI

• Direct binding of chromosome axis and cohesin complexes underlies meiotic chromosome architecture in fungi and plants

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-20

  articleOpen accessSenior authorCorresponding

  Abstract In prophase of meiosis I, the proteinaceous chromosome axis provides a scaffold for the compaction of chromosomes into a linear loop array, controls the formation of interhomolog crossovers, and finally becomes integrated into the synaptonemal complex after crossovers have formed. Despite its fundamental importance, how the proteins of the meiotic chromosome axis - meiotic HORMADs, axis core proteins, and cohesin complexes - self-assemble with one another is incompletely understood. In particular, it remains unknown how cohesin complexes interact with other axis components. Here, we combine genetics in S. cerevisiae , AlphaFold-based protein interaction screens, and biochemical assays to reveal that the S. cerevisiae axis core protein Red1 binds the C-terminal winged helix domain of cohesin’s meiosis-specific subunit Rec8. We find that this interaction is conserved across fungi and plants, but not in mammals, suggesting that different eukaryotic phyla use distinct protein-protein interfaces to assemble the chromosome axis.

  PublisherOA PDFDOI

• Chromosome axis protein SYCP2 recruits HORMAD2 to enable meiotic synapsis quality control in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-06

  articleOpen access

  Abstract Faithful chromosome segregation during meiosis depends on accurate recombination and synapsis of homologous chromosomes. These processes are monitored in mammals by checkpoint mechanisms involving the meiotic HORMA-domain proteins HORMAD1 and HORMAD2, which bind unsynapsed chromosome axes and promote activation of the DNA damage–response kinase ATR independently of DNA double-strand breaks (DSBs). However, no mechanism for axis recruitment of HORMAD1 or HORMAD2 had been demonstrated, nor had its role in checkpoint function been tested. We establish that a putative HORMAD-interacting region—the closure motif (CM)—within the chromosome-axis component SYCP2 is selectively required for HORMAD2, but not HORMAD1, localization. Deletion of the SYCP2 CM disrupts SYCP2–HORMAD2 complexes and prevents HORMAD2 axis binding without affecting axis assembly or recombination. Consequently, ATR accumulation and signaling on unsynapsed axes are reduced, and the prophase checkpoint malfunctions in a sexually dimorphic manner—causing aberrant elimination of synapsis-proficient spermatocytes and persistence of asynaptic oocytes. The phenotypes of SYCP2-CM–deficient and HORMAD2-null mice are indistinguishable, establishing the requirement for HORMAD2 axis recruitment in synapsis surveillance. We propose that axial recruitment generates a HORMAD2 scaffold that drives clustering-mediated ATR network activation independently of DSBs, thereby linking chromosome-axis architecture to synapsis quality control in mammalian meiosis.

  PublisherOA PDFDOI

• The phage nucleus synergizes with an anti-defense protein to resist bacterial immunity

  Cell Reports · 2026-04-01

  articleOpen access

  Chimallivirus bacteriophages enclose their replicating genomes in a protein-based compartment termed the phage nucleus. While the phage nucleus segregates phage DNA from host immune proteins, it is not known if additional factors are required to protect against DNA-targeting host defenses. Here, we identify a chimallivirus-encoded DarG2-like antitoxin that localizes to the phage nucleus and provides protection against phage-targeting DarTG2 toxin-antitoxin systems. This protein, which we term AdfM (anti-darT factor macro), contains a macrodomain and removes DarT2-mediated ADP-ribose modifications from DNA. In the absence of AdfM, DarT2 modifies phage DNA and restricts chimallivirus replication despite being largely excluded from the phage nucleus. Increasing the nuclear concentration of DarT2 while decreasing the nuclear concentration of AdfM reduces phage replication. These results show that the phage nucleus is insufficient to completely protect the chimallivirus genome from host defenses; rather, it is one component of a multilayered counter-defense strategy.

  PublisherDOI

• Molecular mechanism of a single stranded DNA-stimulated bacterial immune peptidase

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-18

  articleSenior author

  Bacteria encode hundreds of immune pathways that protect host cells against infection by bacteriophages. While immune pathways possess exquisite mechanisms for self-regulation to avoid aberrant activation, many are also tightly regulated at the level of transcription. Many immune operons are regulated by CapP+CapH, a two-protein transcriptional regulator system that triggers immune operon expression in response to DNA damage, by sensing the presence of single-stranded DNA byproducts of DNA damage repair. Here we define how the CapP peptidase is activated by single-stranded DNA. DNA binding in a conserved inter-domain groove in CapP triggers rearrangement of the autoregulatory "cysteine switch loop", opening the active site and allowing binding and cleavage of CapH, which in turn leads to transcriptional activation of an associated immune operon. Our data define a conserved molecular mechanism for sensing bacteriophage infection via DNA damage, and for triggering increased expression of immune operons in response.

  PublisherDOI

• Engineered OAA lectins as selective and sensitive high mannose glycan targeting tools

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-06

  articleOpen access

  Abstract The Oscillatoria agardhii agglutinin (OAA) lectin interacts with N-glycans through a pentamannose core shared among all high mannose N-glycans (HMGs). Because HMGs only differ by number of mannose sugars, there is a scarcity of tools sensitive enough to resolve each specific HMG structure in their biological context. Here, we investigate the sequence space of OAA to tune the binding properties towards selectivity of Man 5 GlcNAc 2 , thus generating a structure-specific detection tool. Using phage display to screen a diverse library of OAA variants, we identify a variant with high selectivity for Man 5 GlcNAc 2 that we further dissect to reveal four mutations necessary for selectivity and two mutations responsible for enhanced affinity for all HMGs. Coupling a crystal structure of the selective variant with binding analysis of specific point mutations, we reveal how co-dependent mutations achieve selectivity. We then demonstrate how variants can be valency-modulated on a single beta-barrel scaffold to improve their binding properties by orders of magnitude. Finally, we showcase the applicability of engineered OAA variants as improved HMG profiling tools and tunable antiviral agents.

  PublisherDOI

• Meet the author: Kevin Corbett

  Structure · 2026-03-01

  article1st authorCorresponding
  PublisherDOI

• SCEP3 initiates synapsis and implements crossover interference in Arabidopsis

  Nature Plants · 2025-11-18 · 2 citations

  articleOpen access

  The synaptonemal complex (SC) is a meiosis-specific tripartite proteinaceous structure that regulates the number and positions of crossovers (COs). Here we characterize SCEP3, a new Arabidopsis SC component that is essential for CO assurance, promoting positive CO interference and preventing negative CO interference. SCEP3 localizes to the chromosome axes as numerous foci at leptotene, of which a small proportion cluster as large foci that initiate synapsis. SCEP3 then relocates to the central region of the SC as ZYP1 polymerizes. In the absence of SCEP3, homologues align but do not synapse. In the scep3 mutants, COs increase in number towards the chromosome ends and are more likely to cluster together. SCEP3 encodes an 801-amino-acid intrinsically disordered protein that is structurally similar to SIX6OS1 in mammals and SYP-4 in nematodes, containing phenylalanine repeats at the amino terminus and a carboxy-terminal coiled-coil, suggesting that it is a fundamentally conserved SC component across kingdoms.

  PublisherDOI

Recent grants

• Molecular mechanisms of nucleic acid recognition and maintenance in meiosis and innate immunity

  NIH · $2.7M · 2022–2026

• Functional RNA elements in the human genome

  NIH · $12.4M · 2026–2030

• Expanding the CRISPR/Cas toolbox for RNA modulation

  NIH · $863k · 2018–2023

• Molecular mechanisms of the first-identified bacterial HORMA and Pch2-like proteins in a novel second-messenger signaling pathway

  NIH · $409k · 2020–2021

• Molecular mechanisms of chromosome organization and recombination control by the meiotic chromosome axis

  NIH · $3.1M · 2012–2023

Frequent coauthors

• Qiaozhen Ye

  University of California, San Diego

  47 shared

• Jennifer A. Doudna

  University of California, Berkeley

  29 shared

• Elizabeth Villa

  University of California, San Diego

  26 shared

• Amar Deep

  25 shared

• Joe Pogliano

  University of California, San Diego

  24 shared

• Scott Rosenberg

  24 shared

• Arshad Desai

  Ludwig Cancer Research

  20 shared

• Rebecca Lau

  19 shared