Dr. Crickard is using high-throughput single molecule imaging to rebuild and visualize the process of homologous recombination (HR) in real time. DNA is subjected to many insults leading to damage. This DNA damage leads to a loss in genomic integrity, resulting in the formation and metastasis of many types of cancer. To guard against DNA damage, cells have developed several complex regulatory networks devoted to repair of damaged DNA, including HR. HR involves the search and pairing of one damaged piece of DNA to similar or identical DNA sequences to promote repair of the damaged piece, thus maintaining genome integrity. He seeks to understand, at the most basic biochemical level, how two of the key protein components in HR, Rad51 and Rad54, function to find and repair damaged DNA. His findings will give new insights into how cells fix damaged DNA, which may be key to the development of novel treatments and therapeutic options for all types of cancer.
Content courtesy of Damon Runyon Cancer Research Foundation
Crickard JB, Kaniecki K, Kwon Y, Sung P, Greene EC. Spontaneous self-segregation of Rad51 and Dmc1 DNA recombinases within mixed recombinase filaments. J Biol Chem. 2018.
Crickard JB, Kaniecki K, Kwon Y, Sung P, Lisby M, Greene EC. Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific presynaptic complex. EMBO J. 2018.
Crickard JB, Kaniecki K, Kwon Y, Sung P, Greene EC. Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase. Proc Natl Acad Sci U S A. 2018.
Crickard JB, Greene EC. Biochemical attributes of mitotic and meiotic presynaptic complexes. DNA Repair (Amst). 2018.
Crickard JB, Greene EC. The biochemistry of early meiotic recombination intermediates. Cell Cycle. 2018.
Crickard JB, Kwon Y, Sung P, Greene EC. Dynamic interactions of the homologous pairing 2 (Hop2)-meiotic nuclear divisions 1 (Mnd1) protein complex with meiotic presynaptic filaments in budding yeast. J Biol Chem. 2019.
Xue C, Wang W, Crickard JB, Moevus CJ, Kwon Y, Sung P, Greene EC. Regulatory control of Sgs1 and Dna2 during eukaryotic DNA end resection. Proc Natl Acad Sci U S A. 2019.
Crickard JB, Greene EC. Helicase Mechanisms During Homologous Recombination in Saccharomyces cerevisiae. Annu Rev Biophys. 2019.
Crickard JB, Xue C, Wang W, Kwon Y, Sung P, Greene EC. The RecQ helicase Sgs1 drives ATP-dependent disruption of Rad51 filaments. Nucleic Acids Res. 2019.
Steinfeld JB, Beláň O, Kwon Y, Terakawa T, Al-Zain A, Smith MJ, Crickard JB, Qi Z, Zhao W, Rothstein R, Symington LS, Sung P, Boulton SJ, Greene EC. Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination. Genes Dev. 2019.
Yan Z, Xue C, Kumar S, Crickard JB, Yu Y, Wang W, Pham N, Li Y, Niu H, Sung P, Greene EC, Ira G. Rad52 Restrains Resection at DNA Double-Strand Break Ends in Yeast. Mol Cell. 2019.
Crickard JB, Moevus CJ, Kwon Y, Sung P, Greene EC. Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination. Cell. 2020.
Crickard JB, Kwon Y, Sung P, Greene EC. Rad54 and Rdh54 occupy spatially and functionally distinct sites within the Rad51-ssDNA presynaptic complex. EMBO J. 2020.
Meir A, Crickard JB, Kwon Y, Sung P, Greene EC. Rad54 and Rdh54 prevent Srs2-mediated disruption of Rad51 presynaptic filaments. Proc Natl Acad Sci U S A. 2022.