Megan C. King, PhD
Associate Professor of Cell Biology and of Molecular, Cellular and Development Biology; Co-Leader, Radiobiology and Genome Integrity, Yale Cancer Center; Associate Cancer Center Director, Basic Science
Research & Publications
Biography
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Research Summary
Our laboratory is interested in the fundamental mechanisms that control nuclear mechanics, dynamics, and quality control.
Major efforts in our group include:
- Developing a quantitative model for the mechanical response of the nucleus.
- Investigating how nuclear compartments and local chromatin state influence genome integrity mechanisms.
- Defining how the genome is organized over time in single cells.
- Defining contexts in which direct mechanotransduction of force through the LINC complex regulates cell function and homeostasis.
Specialized Terms: Nucleus; Nuclear envelope; DNA repair; Cellular mechanics; Genome organization
Extensive Research Description
One major focus is on macromolecular complexes embedded in the nuclear envelope physically couple the cytoskeleton to the nucleus (LINC complexes). We seek to define the fundamental mechanisms underlying the nuclear force response and the contexts in which direct force transduction to the nuclear lamina impacts cell function using fission yeast, cell culture and mouse models.
We also have a major effort in defining how the genome is organized, taking advantage of insights from chromatin dynamics. Using live cell assays that we have developed, we also investigate how nuclear cell biology impinges on genome integrity.
Coauthors
Research Interests
Cell Nucleus; Cell Biology; DNA Repair; Microtubules; Nuclear Envelope; Telomere
Selected Publications
- Loops and the activity of loop extrusion factors constrain chromatin dynamicsBailey M, Surovtsev I, Williams J, Yan H, Yuan T, Li K, Duseau K, Mochrie S, King M. Loops and the activity of loop extrusion factors constrain chromatin dynamics. Molecular Biology Of The Cell 2023, 34: ar78. PMID: 37126401, PMCID: PMC10398873, DOI: 10.1091/mbc.e23-04-0119.
- RNA-DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission YeastHu Y, Bennett HW, Liu N, Moravec M, Williams JF, Azzalin CM, King MC. RNA-DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast. Genetics 2019, 213: genetics.302606.2019. PMID: 31405990, PMCID: PMC6781888, DOI: 10.1534/genetics.119.302606.
- Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosisStewart RM, Rodriguez EC, King MC. Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis. Molecular Biology Of The Cell 2019, 30: 1664-1675. PMID: 31091167, PMCID: PMC6727752, DOI: 10.1091/mbc.e18-07-0438.
- Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and DiseaseStewart R, King M, Horsley V. Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease. 2018, 263-292. DOI: 10.1007/978-3-319-16769-5_11.
- Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaksLeland BA, Chen AC, Zhao AY, Wharton RC, King MC. Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks. ELife 2018, 7: e33402. PMID: 29697047, PMCID: PMC5945276, DOI: 10.7554/elife.33402.
- The Molecular Composition and Function of the Nuclear Periphery and Its Impact on the GenomeLusk C, King M. The Molecular Composition and Function of the Nuclear Periphery and Its Impact on the Genome. 2018, 35-62. DOI: 10.1007/978-3-319-71614-5_2.
- TeloPCR‐seq: a high‐throughput sequencing approach for telomeresBennett HW, Liu N, Hu Y, King MC. TeloPCR‐seq: a high‐throughput sequencing approach for telomeres. FEBS Letters 2016, 590: 4159-4170. PMID: 27714790, PMCID: PMC5561429, DOI: 10.1002/1873-3468.12444.
- Improved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane ReconstructionZhao Y, Schreiner SM, Koo PK, Colombi P, King MC, Mochrie SG. Improved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane Reconstruction. Biophysical Journal 2016, 111: 19-24. PMID: 27410730, PMCID: PMC4945324, DOI: 10.1016/j.bpj.2016.05.036.
- The tethering of chromatin to the nuclear envelope supports nuclear mechanicsSchreiner SM, Koo PK, Zhao Y, Mochrie SG, King MC. The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nature Communications 2015, 6: 7159. PMID: 26074052, PMCID: PMC4490570, DOI: 10.1038/ncomms8159.
- Nuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesionsStewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. Journal Of Cell Biology 2015, 209: 403-418. PMID: 25963820, PMCID: PMC4427780, DOI: 10.1083/jcb.201502024.
- A Role for Nuclear Envelope Bridging Complexes in Homology-Directed RepairSwartz RK, Rodriguez EC, King MC. A Role for Nuclear Envelope Bridging Complexes in Homology-Directed Repair. Molecular Biology Of The Cell 2014, 25: mbc.e13-10-0569. PMID: 24943839, PMCID: PMC4142617, DOI: 10.1091/mbc.e13-10-0569.
- The KASH protein Kms2 coordinates mitotic remodeling of the spindle pole bodyWälde S, King MC. The KASH protein Kms2 coordinates mitotic remodeling of the spindle pole body. Journal Of Cell Science 2014, 127: 3625-3640. PMID: 24963130, PMCID: PMC4132395, DOI: 10.1242/jcs.154997.
- A Network of Nuclear Envelope Membrane Proteins Linking Centromeres to MicrotubulesKing MC, Drivas TG, Blobel G. A Network of Nuclear Envelope Membrane Proteins Linking Centromeres to Microtubules. Cell 2008, 134: 427-438. PMID: 18692466, PMCID: PMC2617791, DOI: 10.1016/j.cell.2008.06.022.
- Karyopherin-mediated import of integral inner nuclear membrane proteinsKing MC, Lusk C, Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature 2006, 442: 1003-1007. PMID: 16929305, DOI: 10.1038/nature05075.