DNA Double-Strand Breaks Repair in Human Diseases - Pathophysiology and Implications for Therapy Based on Synthetic Lethality

Dear Colleagues,

DNA double-strand breaks (DSBs) are classified as one of the most serious DNA lesions. Unrepaired or miss-repaired DSBs potentially lead to genetic instability and/or even cell death. To survive and maintain normal phenotype cells have evolved specific pathways – collectively named the DNA-damage response (DDR) – to detect and repair DNA lesions. The part of DDR dealing with DSBs consist of two major, canonical  pathways: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). Also, cells capacity to deal with DSBs are supplemented by non-canonical pathways like microhomology-mediated end joining (MMEJ, also known as alternative NHEJ; alt-NHEJ, backup NHEJ) and single strand annealing (SSA). Given the role of these cellular pathways to maintain genetic stability it is clear that any malfunction will resulted in pathological phenotypes on cellular, tissue or whole organisms levels. A classic example, but not the exclusive one are cancers where NHEJ or HRR pathways are often disrupted or deregulated and non-canonical DSBs repair pathways rule the roost which increases genomic instability, consequently promoting cancer progression. These creates excellent therapeutic opportunity as DSBs repair components are promising target to be exploited by synthetic lethality approaches for the use of DDR inhibitors such as PARP inhibitors. It should be mentioned that using our knowledge about DSBs repair for therapeutical purposes are not limited only to cancers. For example human pathogens like Mycobacteria employ DSBs repair to survive during the pathogenic cycle. Moreover, deregulations of DSBs repair are reported in various auto-immunological diseases. This Special Issue objectives to provide novel insights into the molecular and cellular mechanisms underlying DSBs repair in the etiology of human diseases and to show novel therapeutic perspectives within DSBs repair.

Prof. Ireneusz Majsterek
Dr. Tomasz Poplawski
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.