Molecular determinants of G2/M DNA synthesis

RNA Pol II transcription and DNA replication are the two essential processes that use the DNA in our cells as a substrate, allowing them to express the content of their genetic information and to propagate these instructions to daughter cells. However, the DNA can be engaged only by one of these processes at any given time, and we know that transcription can impair DNA replication inducing DNA damage and genome instability. Indeed, we recently discovered that also during the replication of genes transcription is still active, and consequently these regions are skipped and not replicated efficiently. Often, once a region is skipped it remains under-replicated throughout the cell cycle, becoming definitely duplicated only once cells are preparing for mitosis, in G2/M. This G2/M DNA synthesis (G-MiDS) is highly frequent in cells but not associated with sites of DNA damage nor regulated by canonical DNA damage repair factors, making it a totally new process. Importantly, it is an essential process for cells, as interfering with G-MiDS leads to an increase of mitotic problems, and G-MiDS sites overlap with hotspots of rearrangements identified in cancer cells. Altogether, we intend understanding what G-MiDS is, what factors are involved in this process, and the consequences for transcription and genome instability if G-MiDS is affected.