Mark Hedglin
Assistant Professor of Chemistry; Assistant Professor of Biochemistry and Molecular Biology
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210A Wartik Lab
University Park, PA 16802 - muh218@psu.edu
- 814-863-1080
Research Summary
Deciphering how efficient and faithful replication of the human genome is achieved within the highly-complex, dynamic, and reactive environment of the nucleus. Identifying pathways for genomic instability in humans, identifying novel oncogenic drug targets, developing better chemotherapeutic treatments for human cancers caused by genomic instability.
Huck Graduate Students
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Most Recent Publications
Replicative DNA Polymerase Epsilon and Delta Holoenzymes Show Wide Ranging Inhibition at G-Quadruplexes in the Human Genome
Suzanne Hile, Matthias Weissensteiner, Kara Pytko, Joseph Dahl, Eduard Kejnovsky, Iva Kejnovska, Mark Hedglin, IIias Georgakopoulos-Soares, Kateryna Makova, Kristin Eckert, 2025, Nucleic Acids Research
Cryo-EM structure of apo-form human DNA polymerase δ elucidates its minimal DNA synthesis activity without PCNA
Yeonoh Shin, Mark Hedglin, Katsuhiko Murakami, 2025, Journal of Biological Chemistry
PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress
Daniela Muoio, Natalie Laspata, Rachel L. Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel, 2024, Nature Communications
Replication protein A dynamically re-organizes on primer/template junctions to permit DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis
Jessica L. Norris, Lindsey O. Rogers, Kara G. Pytko, Rachel L. Dannenberg, Samuel Perreault, Vikas Kaushik, Sahiti Kuppa, Edwin Antony, Mark Hedglin, 2024, Nucleic Acids Research on p. 7650-7664
Replication of [AT/TA]<sub>25</sub> Microsatellite Sequences by Human DNA Polymerase δ Holoenzymes Is Dependent on dNTP and RPA Levels
Kara G. Pytko, Rachel L. Dannenberg, Kristin A. Eckert, Mark Hedglin, 2024, Biochemistry
Direct, ensemble FRET approaches to monitor transient state kinetics of human DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis
Jessica L. Norris, Mark Hedglin, 2024, on p. 271-309
Stepwise requirements for polymerases δ and θ in theta-mediated end joining
Susanna Stroik, Juan Carvajal-Garcia, Dipika Gupta, Alyssa Edwards, Adam Luthman, David W. Wyatt, Rachel L. Dannenberg, Wanjuan Feng, Thomas A. Kunkel, Gaorav P. Gupta, Mark Hedglin, Richard Wood, Sylvie Doublié, Eli Rothenberg, Dale A. Ramsden, 2023, Nature on p. 836-841
Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics
Nicole M. Hoitsma, Jessica Norris, Thu H. Khoang, Vikas Kaushik, Rahul Chadda, Edwin Antony, Mark Hedglin, Bret D. Freudenthal, 2023, Nucleic Acids Research on p. 6738-6753
Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities
Rachel L. Dannenberg, Joseph A. Cardina, Kara G. Pytko, Mark Hedglin, 2022, Nucleic Acids Research on p. 9893-9908
Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch
Christl Gaubitz, Xingchen Liu, Joseph Magrino, Nicholas P. Stone, Jacob Landeck, Mark Hedglin, Brian A. Kelch, 2020, Proceedings of the National Academy of Sciences of the United States of America on p. 23571-23580
Most-Cited Papers
Regulation of Rad6/Rad18 Activity during DNA Damage Tolerance
Mark Hedglin, Stephen J. Benkovic, 2015, Annual Review of Biophysics and Biomolecular Structure on p. 207-228
Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis
Mark Hedglin, Binod Pandey, Stephen J. Benkovic, 2016, Proceedings of the National Academy of Sciences of the United States of America on p. E1777-E1786
Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique Detours around the Same Obstacle
Mark Hedglin, Stephen J. Benkovic, 2017, Chemical Reviews on p. 7857-7877
Characterization of human translesion DNA synthesis across a UV-induced DNA lesion
Mark Hedglin, Binod Pandey, Stephen J. Benkovic, 2016, eLife
Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch
Christl Gaubitz, Xingchen Liu, Joseph Magrino, Nicholas P. Stone, Jacob Landeck, Mark Hedglin, Brian A. Kelch, 2020, Proceedings of the National Academy of Sciences of the United States of America on p. 23571-23580
Replication protein A dynamically regulates monoubiquitination of proliferating cell nuclear antigen
Mark Hedglin, Mahesh Aitha, Anthony Pedley, Stephen Benkovic, 2019, Journal of Biological Chemistry on p. 5157-5168
Replication Protein A Prohibits Diffusion of the PCNA Sliding Clamp along Single-Stranded DNA
Mark Hedglin, Stephen J. Benkovic, 2017, Biochemistry on p. 1824-1835
Monitoring the Retention of Human Proliferating Cell Nuclear Antigen at Primer/Template Junctions by Proteins That Bind Single-Stranded DNA
Mark Hedglin, Mahesh Aitha, Stephen J. Benkovic, 2017, Biochemistry on p. 3415-3421
Probing the DNA structural requirements for facilitated diffusion
Mark Hedglin, Yaru Zhang, Patrick J. O'Brien, 2015, Biochemistry on p. 557-566
Stepwise requirements for polymerases δ and θ in theta-mediated end joining
Susanna Stroik, Juan Carvajal-Garcia, Dipika Gupta, Alyssa Edwards, Adam Luthman, David W. Wyatt, Rachel L. Dannenberg, Wanjuan Feng, Thomas A. Kunkel, Gaorav P. Gupta, Mark Hedglin, Richard Wood, Sylvie Doublié, Eli Rothenberg, Dale A. Ramsden, 2023, Nature on p. 836-841