Research - Institute of Genetics - Genome Instability and Carcinogenesis Unit - Laboratory of Replication and Genom Stability

Péter BURKOVICS
senior research associate

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Enikő Ilona KÖRMÖCZINÉ DR. SAJBEN-NAGY research associate
Ágnes TÓTH Ph.D. student
Karola Edit ALMÁSI Ph.D. student

LABORATORY OF REPLICATION AND GENOM STABILITY

Replication of the genetic information is essential for all organisms; incorrect replication may lead to cancer formation in humans. Therefore, it is very important to understand how the integrity of the genome is preserved during replication. The replication process can be perturbed by several circumstances such as damaged template DNA or a stable secondary structure of single-stranded DNA, resulting in the stalling of the replication fork.

In our laboratory, we focus on the replication of DNA regions that are able to form stable secondary structures. The most well-studied form of stable secondary DNA structures is the G quadruplex (G4) structure. This is a planar tetrameric structure formed by Hoogsteen base pairing between the guanines. The consensus sequence which can potentially form a G quadruplex structure is (G3-5–N1-7))4. In the human genome, more than 360000 potentially G4-forming sequences can be found. The G4-forming sequences can be classified into two groups: in one of them the structures are present at the ends of the chromosomes and form the telomeres, which are responsible for the stability of the chromosome ends; in the members of the other group, which is not well-characterized in details yet, the structures are located in the intrachromosomal regions of the chromosomes. Recently, these intrachromosomal G4 sequences have been shown to play an important function in the regulation of transcription and translation, in the firing of replication origins, and in the formation of recombination hot spots. Therefore, their precise replication is essential; failed replication may result in altered gene expression regulation and replication leading to the loss of genome integrity and oncogenic activation.

In our laboratory, we analyze the mechanisms of G4 replication using Saccharomyces cerevisiae as a model organism in in vivo experiments and biochemical assays to identify and characterize the key players of this process.

Selected publications

Toth, A., Hegedus, L., Juhasz, S., Haracska, L. & Burkovics, P. (2017) The DNA-binding box of human SPARTAN contributes to the targeting of Poleta to DNA damage sites, DNA repair. 49, 33-42.

Burkovics, P., Dome, L., Juhasz, S., Altmannova, V., Sebesta, M., Pacesa, M., Fugger, K., Sorensen, C. S., Lee, M. Y., Haracska, L. & Krejci, L. (2016) The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis, Nucleic acids research. 44, 3176-89

Baldeck, N., Janel-Bintz, R., Wagner, J., Tissier, A., Fuchs, R. P., Burkovics, P., Haracska, L., Despras, E., Bichara, M., Chatton, B. & Cordonnier, A. M. (2015) FF483-484 motif of human Poleta mediates its interaction with the POLD2 subunit of Poldelta and contributes to DNA damage tolerance, Nucleic acids research. 43, 2116-25.

Burkovics, P., Sebesta, M., Balogh, D., Haracska, L. & Krejci, L. (2014) Strand invasion by HLTF as a mechanism for template switch in fork rescue, Nucleic acids research. 42, 1711-20.

Sebesta, M., Burkovics, P., Juhasz, S., Zhang, S., Szabo, J. E., Lee, M. Y., Haracska, L. & Krejci, L. (2013) Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans, DNA repair. 12, 691-8.

Burkovics, P., Sebesta, M., Sisakova, A., Plault, N., Szukacsov, V., Robert, T., Pinter, L., Marini, V., Kolesar, P., Haracska, L., Gangloff, S. & Krejci, L. (2013) Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis, The EMBO journal. 32, 742-55.

Sebesta, M., Burkovics, P., Haracska, L. & Krejci, L. (2011) Reconstitution of DNA repair synthesis in vitro and the role of polymerase and helicase activities, DNA repair. 10, 567-76.