Publication of the Laboratory of Structural Biology in the Prestigious Nucleic Acids Research Journal
We are pleased to inform you that the article titled "Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps" (doi: 10.1093/nar/gkaf099) has been published in the prestigious scientific journal Nucleic Acids Research. The journal boasts an impact factor (IF) of 16.7!
This publication is the result of a collaboration between the team of the Laboratory of Structural Biology, headed by Dr. hab. Michał R. Szymański, Professor at the University of Gdańsk, and the group of Prof. Dr. hab. inż. Jacek Czub from the Gdańsk University of Technology. The authors of the publication are: Dr. Anna Karłowicz, Dr. Andrzej B. Dubiel, M.Sc. Marta Wyszkowska, Dr. Kazi Amirul Hossain, Prof. Dr. hab. inż. Jacek Czub, and Dr. hab. Michał R. Szymański, Professor at the University of Gdańsk (corresponding author).
Single-stranded DNA (ssDNA) is an important intermediate generated during various cellular DNA transactions, primarily during long-patch base excision repair. When displaced by DNA polymerase during strand displacement DNA synthesis, ssDNA forms 5′ overhangs (flaps) that are either cleaved by DNA nucleases or protected from degradation upon binding of single-stranded DNA binding proteins (SSB). There are several nucleases implicated in ssDNA flaps removal in human mitochondria, namely endonucleases FEN1 and DNA2 as well as exonuclease MGME1. In this study, we show that another mitochondrial nuclease, EXOG, cleaves DNA flaps in both free and SSB-protected forms. We established that the presence of the Wing domain in EXOG structure provides additional binding site for ssDNA and 5′ flaps irrespective of monovalent salt concentration. Importantly, DNA flap cleavage by EXOG is compatible with the activity of other mitochondrial enzymes involved in DNA replication/repair, e.g., mtSSB, Pol γ and Lig III, as we were able to reconstitute a multistep reaction of DNA synthesis, flap removal and nick ligation. Our findings highlight the versatile role of EXOG in maintaining mitochondrial DNA integrity, adding single-stranded DNA flap removal to the repertoire of its DNA processing activities.