Craig Chen
Undergraduate
Nancy Hollingsworth
Distinguished Teaching Professor
Department of Biochemistry and Cell Biology
My lab studies the regulation and execution of meiotic recombination using the budding yeast, Saccharomyces cerevisiae. Meiosis is the specialized cell division that divides the chromosome number in half to make haploid gametes for sexual reproduction. During meiosis, replicated chromosomes undergo two divisions: at Meiosis I, homologous chromosomes segregate to opposite poles of the spindle, while sister chromatids segregate at Meiosis II. Meiosis is a highly conserved process and many of the genes necessary for meiosis in yeast are also required for mammalian meiosis. My lab uses genetic, molecular biological, biochemical and cytological approaches to identify and characterize genes important in meiosis.
Meiotic recombination creates crossovers between homologous chromosomes that, in combination with sister chromatid cohesion, allow the pairs of homologs to segregate properly at the first meiotic division. Meiotic recombination is initiated by the introduction of programmed double strand breaks that are then processed to produce either crossover or noncrossover chromosomes. The repair of these double strand breaks is regulated. The major questions that my lab is currently trying to answer are:
- What are the roles that the conserved Sen1 DNA/RNA helicase plays during premeiotic S phase and meiotic recombination? Sen1 can disassemble DNA/RNA hybrids that form either during premeiotic S phase or on the resected ends of meiotic double strand breaks.
- The successful completion of interhomolog recombination during prophase I of meiosis results in the formation of a structure that connects pairs of homologous chromosomes called the synaptonemal complex. Any remaining double strand breaks must be then be repaired before chromosomes segregate at the first meiotic division. My lab is interested in identifying the genes that mediate this repair and the mechanisms by which this repair occurs.
Dutta, R., D. Murtha, T. Nagosky, and N. M. Hollingsworth (2026) Residual double strand repair during meiosis in budding yeast is promoted by PIF1, RAD54 and RDH54/TID1. Genetics: doi: 10.1093/genetics/iyag115.
Gaglione, R., J. Caradonna, A. J. MacQueen, E. Luk and N. M. Hollingworth (2025) The conserved SEN1 DNA/RNA helicase has multiple functions during yeast meiosis. PLoS Genetics 21(12): e1011684 https//doi.org/10.1371/journal.pgen. 1011684
Weng, Q, L. Wan, G.C. Straker, T. D. Deegan, B. P. Duncker, A. M. Neiman, E. Luk and N. M. Hollingsworth (2024) An acidic loop in the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates Genetics 228: https://doi.org/10.1093/genetics/iyae106.
Ziesel, A., Q. Weng, J. S. Ahuja, A. Bhattacharya, R. Dutta, E. Cheng, G. V. Börner, M. Lichten and N. M. Hollingsworth (2022) Rad51-mediated interhomolog recombination during budding yeast meiosis is promoted by the meiotic recombination checkpoint and the conserved Pif1 helicase. PLoS Genetics 18:e1010407. doi:10.1371/journal.pgen1010407.
Hollingsworth, N. M. (2020) A new role for the synaptonemal complex in the regulation of meiotic recombination. Genes Dev. 34: 1562-1564. doi: 10.1101/gad34588.120.
Hollingsworth, N. M. and R. Gaglione (2019) The meiotic-specific Mek1 kinase in budding yeast regulates interhomolog recombination and coordinates meiotic progression with double strand break repair. Current Genetics https://doi.org/10.1007/s00294-019-00937-3.
Chen, X.*, R. Gaglione*, T. Leong, L. Bednor, T. de lost Santos, E. Luk, M. Airola and N. M. Hollingsworth, (2018) Mek1 coordinates meiotic progression with DNA break repair by directly phosphorylating and inhibiting the yeast pachytene exit regulator Ndt80. PLoS Genetics, 14(11):e1007832. doi: 10.1371/journal.pgen.1007832. *co-first authors
Prugar, E.*, C. Burnett*, X. Chen and N. M. Hollingsworth (2017) Coordination of double strand break repair and meiotic progression in yeast by a Mek1-Ndt80 negative feedback loop. Genetics doi: 10.1534/genetics.117.199703 *co-first authors This paper was highlighted in Genetics and was written up in a blog at the Saccharomyces Genome Database website: http://www.yeastgenome.org/meiotic-fail-safes.
Callender, T. L., R. Laureau, L. Wan, X. Chen, R. Sandhu, S. Laljee, S. Zhou, R. T. Suhandynata, E. Prugar, W. A. Gaines, Y. Kwon, G. V. Börner, A. Nicolas, A. M. Neiman and N. M. Hollingsworth (2016) Mek1 down regulates Rad51 activity during yeast meiosis by phosphorylation of Hed1. PLoS Genet 12(8): e1006226. doi:10.1371/journal.pgen.1006226
Chen, X., R. T. Suhandynata, R. Sandhu, B. Rockmill, N. Mohibullah, H. Niu, J. Liang, H-C Lo, D. E. Miller, H. Zhou, G. V. Börner, and N. M. Hollingsworth (2015) Phosphorylation of the synaptonemal complex protein Zip1 regulates the crossover/noncrossover decision during yeast meiosis. PLoS Biol 13(12): e1002329. doi: 10.1371/journal.pbio.1002329
Suhandynata, R., J. Liang, C. P. Albuquerque, H. Zhou and N. M. Hollingsworth (2014) A method for sporulating budding yeast cells that allows for unbiased identification of kinase substrates using stable isotope labeling by amino acids in cell culture. G3 4: 2125-2135.
Liu, Y., W. Gaines, T. Callender, V. Busygina, A. Oke, P. Sung, J. Fung and N. M. Hollingsworth (2014) Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks. PLoS Genet. 10:e1004005 doi:10.1371/journalpgen.1004005
Lo, H.C., R. C. Kunz, X. Chen, A. Marullo, S. P. Gygi and N. M. Hollingsworth (2012) Cdc7-Dbf4 is a gene-specific regulator of Ndt80-activated gene expression during meiosis in yeast. Mol. Cell. Biol. 32: 541-557.
Lo, H.C. and N. M. Hollingsworth (2011) Using the semi-synthetic epitope system to identify direct substrates of the meiosis-specific budding yeast kinase, Mek1. Meth. Mol. Biol. 745: 135-149.
Callender, T. and N. M. Hollingsworth (2010) Mek1 suppression of meiotic double strand break repair is specific to sister chromatids, chromosome autonomous and independent of REC8 cohesin complexes. Genetics 2: 185:1-12.
Niu, H., L. Wan, V. Busygina, Y. Kwon, J. A. Allen, X. Li, R. C. Kunz, K. Kubota, B. Wang, P. Sung, K. M. Shokat, S. P. Gygi and N. M. Hollingsworth (2009) Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation. Mol. Cell 36: 393-404.
Lo, H-C., L. Wan, A. Rosebrock, B. Futcher and N. M. Hollingsworth (2008) Cdc7-Dbf4 regulates NDT80 transcription as well as reductional segregation during budding yeast meiosis. Mol. Biol. Cell. 19: 4956-4967.
Wan, L., H. Niu, B. Futcher, C. Zhang, K. M. Shokat, S. J. Boulton and N. M. Hollingsworth (2008) Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast. Genes Dev. 22: 386-397.
Niu, H., X. Li, E. Job, C. Park, D. Moazed, S. P. Gygi and N. M. Hollingsworth (2007) Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis. Mol. Cell. Biol. 15: 5456-5467.
Wan, L., C. Zhang, K. M. Shokat and N. M. Hollingsworth (2006) Chemical inactivation of Cdc7 kinase in budding yeast results in a reversible arrest that allows efficient cell synchronization prior to meiotic recombination. Genetics 174: 1767-1774.
Niu, H., B. Baumgartner, D. Schaefer, L. Wan, J. Loidl, and N. M. Hollingsworth (2005) Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1. Mol. Biol. Cell 16: 5804-5818.
Wan, L., T. de los Santos, C. Zhang, K. Shokat, N. M. Hollingsworth (2004) Mek1 kinase activity functions downstream of RED1 in the regulation of meiotic DSB repair in budding yeast. Mol. Biol. Cell 15: 11-23.
de los Santos, T., N. Hunter, C. Lee, B. Larkin, J. Loidl, and N. M. Hollingsworth (2003). The Mus81/Mms4 endonuclease acts independently of double Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 164: 81-94.
Woltering, D., B. Baumgartner, S. Bagchi, B. Larkin, J. Loidl, T. de los Santos and N. M. Hollingsworth (2000) Meiotic segregation, synapsis and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p. Mol. Cell. Biol. 20: 6646-6658.
Pochart, P., D. Woltering and N. M. Hollingsworth (1997) Conserved properties between functionally distinct MutS homologs in yeast. J. Biol. Chem. 272: 30345-30349.
Hollingsworth, N. M., L. Ponte and C. Halsey (1995) MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae, but not mismatch repair. Genes Dev. 9: 1728-1739.
