Melike Caglayan,

Laboratory of DNA Repair

The integrity of one’s genetic material is constantly being threatened by a variety of endogenous sources and exogenous factors such as UV-light and environmental agents. Unintended changes to DNA have the potential to lead to permanent alterations in the coding property of the genome or to drive adverse molecular events, such as transcriptional blockage or replication fork collapse.

Fortunately, cells have evolved a suite of mechanisms, known as DNA repair, that aim to recognize and resolve harmful damage, preserving genome integrity and averting disease development.

Base Excision Repair (BER) is the most important process for preventing the mutagenic and lethal consequences of DNA damage. Inherited or sporadic defects in BER have been demonstrated to result in increased cancer predisposition, immunological dysfunction, and many degenerative diseases, including those of the brain.

The Caglayan lab focuses on the mechanism of BER. Our research includes defining the biochemical mechanisms underlying the repair of oxidative DNA damage and understanding the DNA polymerases and DNA ligases that coordinate at the downstream steps using a combined approach including biochemical, biophysical, structural, and single-molecule studies. Research in our group explores the mechanisms of genome stability and the consequences of altered stability for cancer.

Using DNA repair assays in vitro, the Caglayan lab study how the BER proteins coordinate to execute DNA damage processing. Using X-ray crystallography, the Caglayan lab gain an atomic insight into the mechanism of nick sealing by DNA ligase with structure/function studies. By employing a three-color total internal reflection fluorescence (TIRF) microscopy, the Caglayan lab monitor the sequential multi-step process of BER pathway coordination at single-molecule level, and visualize the dynamics of DNA ligation in real-time.

Dr. Caglayan’s research program has been continuously funded by R00 from NIEHS, UF Health Cancer Center, Thomas Maren Award from UF/COM, R35 MIRA ESI from NIGMS. Her laboratory’s work has been recognized by the scientific community via invitations for review articles, talks at national/international conferences, and requests to serve on grant review committees for NIH and NSF.

Key publications:

Published at Nature

1. 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.

2. Çağlayan M*. and Wilson S.H. (2018) Pol μ dGTP mismatch insertion opposite T coupled with ligation reveals a promutagenic DNA intermediate during double strand break repair. Nature Communications 9: 4213. *Co-corresponding author

3. Çağlayan M., Horton J.K., Da-Peng D., Stefanick D.F., Wilson S.H. (2017) Oxidized nucleotide insertion by pol β confounds ligation during base excision repair. Nature Communications 8: 14045.

4. Çağlayan M., Batra V.K., Sassa A., Prasad R., Wilson S.H. (2014) Role of polymerase β in complementing aprataxin deficiency during abasic-site base excision repair. Nature Structural and Molecular Biology 21: 497-499.

Published at Nucleic Acids Research

1. 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.

2. 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.

3. Çağlayan M. (2020) The ligation of polβ mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates. Nucleic Acids Research 8: 3708-3721.

4. Çağlayan M., Prasad R., Krasich R., Longley M.J., Kadoda K., Tsuda M., Sasanuma H., Takeda S., Tano K., Copeland W.C., Wilson S.H. (2017) Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts. Nucleic Acids Research 17: 10079-10088.

5. Çağlayan M., Horton J.K., Prasad R., Wilson S.H. (2015) Complementation of aprataxin deficiency by base excision repair enzymes. Nucleic Acids Research 43: 2271-2281.

6. Çağlayan M., Horton J.K., Prasad R., Wilson S.H. (2015) Complementation of aprataxin deficiency by base excision repair enzymes. Nucleic Acids Research 43: 2271-2281.

7. Çağlayan M., Prasad R., Krasich R., Longley M.J., Kadoda K., Tsuda M., Sasanuma H., Takeda S., Tano K., Copeland W.C., Wilson S.H. (2017) Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts. Nucleic Acids Research 17: 10079-10088.

Published at Journal of Biological Chemistry

1. Balu K., Almohdar D., Tang Q., Ratcliffe J., Kalaycioglu M., Çağlayan M. (2024) Structures of LIG1 uncover the mechanism of sugar discrimination against 5′-RNA-DNA junctions during ribonucleotide excision repair. Journal of Biological Chemistry. 9: 107688.

2. Almohdar D., Murcia M., Tang Q., Ortiz A., Martinez E., Parwal, T., Kamble P., Çağlayan M. (2024) Impact of DNA ligase 1 and IIIα interactions with APE1 and polβ on the efficiency of base excision repair pathway at the downstream steps. Journal of Biological Chemistry. 300: 107355.

3. Balu K., Gulkis M., Almohdar D., Çağlayan M. (2024) Structures of LIG1 provide a mechanistic basis for understanding a lack of sugar discrimination against a ribonucleotide at the 3′-end of nick DNA. Journal of Biological Chemistry. 300: 107216.

4. Tang Q. and Çağlayan M. (2021) The scaffold protein XRCC1 stabilizes the formation of polβ/gap DNA and ligase IIIα/nick DNA complexes in base excision repair. Journal of Biological Chemistry 297: 101025.

5. Kamble P., Hall K., Chandak M., Tang Q., Çağlayan M. (2021) DNA ligase I fidelity the mutagenic ligation of pol β oxidized and mismatch nucleotide insertion products in base excision repair. Journal of Biological Chemistry 296: 100427.

• DNA Repair
• DNA Replication
• DNA damage
• Nucleic acids enzymology
• Single-Molecule Microscopy
• X-ray crystallography