Mark Hedglin

Assistant Professor of Chemistry; Assistant Professor of Biochemistry and Molecular Biology

210A Wartik Lab
University Park, PA 16802
muh218@psu.edu
814-863-1080

Bio & Links
Publications

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

Tyler Wenzel

Huck Affiliations

Molecular, Cellular, and Integrative Biosciences

Center for Structural Biology

Most Recent Publications

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

Structural basis of reiterative transcription from the pyrG and pyrBI promoters by bacterial RNA polymerase

Yeonoh Shin, Mark Hedglin, Katsuhiko S. Murakami, 2020, Nucleic Acids Research on p. 2144-2155

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

Mark Hedglin

Assistant Professor of Chemistry; Assistant Professor of Biochemistry and Molecular Biology

Research Summary

Huck Graduate Students

Huck Affiliations

Links

Most Recent Publications

Cryo-EM structure of apo-form human DNA polymerase δ elucidates its minimal DNA synthesis activity without PCNA

PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress

Replication protein A dynamically re-organizes on primer/template junctions to permit DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis

Replication of [AT/TA]<sub>25</sub> Microsatellite Sequences by Human DNA Polymerase δ Holoenzymes Is Dependent on dNTP and RPA Levels

Direct, ensemble FRET approaches to monitor transient state kinetics of human DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis

Stepwise requirements for polymerases δ and θ in theta-mediated end joining

Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics

Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities

Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch

Structural basis of reiterative transcription from the pyrG and pyrBI promoters by bacterial RNA polymerase

Most-Cited Papers

Regulation of Rad6/Rad18 Activity during DNA Damage Tolerance

Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis

Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique Detours around the Same Obstacle

Characterization of human translesion DNA synthesis across a UV-induced DNA lesion

Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch

Replication protein A dynamically regulates monoubiquitination of proliferating cell nuclear antigen

Replication Protein A Prohibits Diffusion of the PCNA Sliding Clamp along Single-Stranded DNA

Probing the DNA structural requirements for facilitated diffusion

Monitoring the Retention of Human Proliferating Cell Nuclear Antigen at Primer/Template Junctions by Proteins That Bind Single-Stranded DNA

Stepwise requirements for polymerases δ and θ in theta-mediated end joining