Melike Caglayan, PhD
Associate Professor, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center
Full member, Fred & Pamela Buffett Cancer Center
Research focus: Genome stability, DNA damage, DNA repair, DNA replication, biochemistry, X-ray crystallography, single-molecule biophysics
Research
The Caglayan laboratory investigates the mechanisms of DNA repair and how defects in DNA damage processing lead to genome instability and cancer. Key focus of Dr. Caglayan’s research program is to elucidate the molecular mechanism of the base excision repair (BER) pathway at the downstream steps that involve gap filling by DNA polymerase β (polβ) and subsequent nick sealing by DNA ligase 1 (LIG1) and DNA ligase 3α (LIG3α). Using an integrated approach combining biochemistry, X-ray crystallography, and biophysical methods, we aim to define how LIG1 and LIG3α coordinate with replication and repair proteins to ensure accurate DNA ligation to maintain genome integrity.
The Caglayan laboratory have made significant advances and published 20 peer-reviewed research articles at high-profile journals such as Nature Communications, Nucleic Acids Research (x4), and Journal of Biological Chemistry (x6). Biochemical studies revealed that BER can promote genome instability when coordination between polβ and LIG1/LIG3α breaks down at the final step. Key discoveries include revealing how oxidative stress disrupts the DNA ligation step, leading to strand breaks and mutagenic outcomes. Dr. Caglayan’s work has demonstrated that polβ insertion of oxidized nucleotides creates repair intermediates that DNA ligases cannot properly seal—the first evidence that the final ligation step is compromised by oxidative damage. Furthermore, recent work established that the scaffold protein XRCC1 stabilizes repair complexes to facilitate substrate channeling between repair enzymes, preventing toxic repair intermediates.
Using X-ray crystallography, the team solved high-resolution structures of LIG1 and delivered atomic level pictures of the ligase active site engaging with mutagenic DNA substrates containing mismatches or oxidative lesions and uncovered a mechanism of sugar discrimination, revealing at atomic resolution how ligases discriminate between correct and incorrect repair products. These structures further explain how disease-associated ligase mutations enhance cancer susceptibility by allowing ligation of mutagenic intermediates.
The lab also employs single-molecule fluorescence microscopy to study protein-DNA interactions during repair and to directly visualize DNA ligase/nick binding dynamics during oxidative damage processing in real time. Together, this work provides molecular insights into how environmental toxins and oxidative stress compromise genome integrity, offering potential therapeutic targets for cancer prevention and treatment.
Current Lab Members:
- Mohamed Ghoneim, Ph.D – Senior Research Associate
PhD in Biophysics with a focus on characterization of DNA repair protein interactions at single-molecule level, Department of Biochemistry, University of Iowa
- Wen-Ting Chen, Ph.D – Postdoctoral Associate
PhD in Structural Biology with a focus on X-ray Crystallography, Department of Chemistry, University of Florid
- Savanna A. Wallin, Ph.D – Postdoctoral Associate
PhD in Biochemistry and Structural Biology with a focus on structural and biophysical characterization of RPA and RAD52 DNA binding proteins, Department of Biochemistry, University of Nebraska
- Tyrell Rossman, Ph.D – Postdoctoral Associate
PhD in Biochemistry with a focus on stopped-flow kinetic analyses of enzymes, Department of Biochemistry, University of Nebraska-Lincoln
For information on student rotation opportunities please contact Dr. Caglayan at mcaglayan@unmc.edu
Trainee Outcomes:
Postdoctoral Associates
- Surajit Chatterjee (2024 - 2025)
- Kanal E. Balu (2023 - 2025)
- Qun Tang (2019 - 2023)
- Kala Basavannacharya (2020 - 2022)
UF College of Medicine, Biomedical Science Graduate Program
- David Murcia (2021 - 2023)
- Ernesto Martinez (2021 - 2023)
- Danah Almohdar (2021 - 2023)
- Mitchell Gulkis (2022 - 2024)
- Mustafa Kalaycioglu (2023 - 2025)
- Jacob Ratcliffe (2023 - 2025)
- Erick Castro (2023 - 2025)
UF College of Medicine, Biomedical Science Undergraduate Students
- Camden Lerner (2023 - 2025)
- Sharad Patel (2023 - 2025)
- Sanandan Ojha (2023 - 2025)
- Julia Moncrieff (2022 - 2025)
- Tanay Parwal (2021 - 2024)
- Maysen Calzon (2019 - 2021)
- Grace Johnson (2020 - 2022)
- Benjamin Beauchamp (2021 - 2022)
- Kosidinma Oguejiofor (2022 - 2023)
UF College of Medicine, Research Technicians
- Kar Men Lee
- Abigail Ortiz
- Pradnya Kamble
- Kalen Hall
- 2001, BS, Biology, Istanbul University, Turkiye
- 2005, MS, Biochemistry, Bogazici University, Turkiye
- 2010, PhD, Biochemistry, Bogazici University, Turkiye
- 2013-2018, Postdoctoral Fellow, National Institute of Environmental Health Science (NIEHS)/NIH
Research Areas:
- Impact of oxidative stress and environmental toxins on genome stability
- DNA damage processing and repair mechanism in cancer development
- Structural biology of DNA ligases and DNA repair complexes
- Base excision repair pathway coordination between DNA polymerase β and DNA ligases
- Visualizing dynamics of DNA replication and repair in real-time at the single-molecule level
Techniques and training:
- X-ray crystallography
- Cryo-electron microscopy (cryo-EM)
- Protein-DNA and protein-protein interaction studies by Biolayer Interferometry (BLI) and Surface Plasmon Resonance (SPR)
- Enzymology of DNA repair enzymes by rapid-quench flow and stop-flow kinetic analyses
- Single-molecule analysis of DNA repair mechanism by Total Internal Reflection Fluorescence (TIRF) microscopy and optical tweezers
- Balu K., Almahdor D., Lerner C., Ratcliffe J., Tang Q., Parwal T., Prakash A., Çağlayan M. (2025) Processing of DNA strand breaks with oxidatively damaged ends by LIG1. Nucleic Acids Research. 53: gkaf1344.
- Chatterjee S., Chaubet L., Berg A., Mukhortava A., Almohdar D., Ratcliffe J., Gulkis M., Çağlayan M. (2024) Probing nick DNA binding by LIG1 at the single-molecule level. Nucleic Acids Research. 52: 12604-12615.
- Gulkis M., Martinez E., Almohdar D., Çağlayan M. (2024) Unfilled gaps by polβ leads to aberrant ligation by LIG1 at the downstream steps of base excision repair. Nucleic Acids Research. 52: 3810-3822.
- Tang Q., Gulkis M., McKenna R., Çağlayan M. (2022) Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair. Nature Communications 13: 3860.
Appointments:
- 2025 - present: Associate Professor, Eppley Institute, University of Nebraska Medical Center
- 2019 - 2025: Assistant Professor, Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida
- 2016 - 2018: Research Fellow, NIEHS/NIH
- 2020 - present: ASBMB #Discover BMB Graduate and Early-career Faculty Travel Award Committee
- 2024 - present: Chair, EMGS Awards and Honors Committee
- Member, American Association for Cancer Research (AACR)
- Member, American Society for Biochemistry and Molecular Biology (ASBMB)
- Member, American Chemical Society (ACS)
- Member, Environmental Mutagenesis and Genomics Society (EMGS)
Honors & Awards
- 2024: UF Health Cancer Center Rising Star of the Year Award
- 2022: ASBMB Early Career Award
- 2020: UF College of Medicine Thomas H. Maren Junior
Investigator Award
- 2019: EMGS Young Scientist Award
- 2015: NIH Pathway to Independence Award K99/R00
Grants
- 2022 - 2027: NIGMS - R35 – Maximizing Investigators' Research Award for Early-Stage Investigators (MIRA ESI). DNA ligase activities during base excision repair coordination. Role: PI
- 2020 - 2022: University of Florida, College of Medicine Thomas Maren Junior Investigator Award. Structural and mechanistic studies of base excision repair. Role: PI
- 2018 - 2022: NIEHS – Pathway to Independence Award (K99/R00) R00ES026191. Oxidant and environmental toxicant-induced effects compromise ligation in DNA repair. Role: PI
University of Nebraska Medical Center
986805 Nebraska Medical Center
Omaha, NE 68198-6805