About this Research Topic
The stability of the nuclear genome encompasses chemical reactions and molecular processes involving DNA and RNA metabolism during the life cycle of cells. Three key mechanisms – DNA replication, telomere maintenance, and DNA repair – confer cells the ability to transmit their genomic information through generations. Some of these molecular pathways share important components and work dynamically, forming intricate networks that act like molecular gears.
DNA replication is an essential and tightly regulated process that follows several ordered steps, leading to new DNA synthesis in S phase of the cell cycle. Replication is triggered after licensing of origins by the accumulation of initiator factors from the end of mitosis through the G1 phase. Subsequently, origins are activated, and specific DNA helicases open the double stranded DNA helix, allowing replication initiation per se. During replication, DNA polymerases copy the parental DNA strands using RNA as a primer, with two forks moving away from the licensed origins. However, due to the inability of DNA polymerase to initiate DNA synthesis at the ends of linear chromosomes – the telomeres –sequence would be lost with each replication round. This problem is circumvented by telomerase, a specialized reverse transcriptase that adds telomeric repeats to the ends of the chromosomes. Without telomerase, progressive shortening of telomeres occurs, leading cells into replicative senescence. Telomerase is a ribonucleoprotein minimally composed of a long non-coding RNA that contains the template sequence copied by the reverse transcriptase protein component during telomere elongation. Telomere maintenance and telomerase activity are controlled by the dynamic action of telomeric proteins that associate with DNA and each other, and with telomeric repeat-containing RNA (TERRA), a long non-coding RNA originating from the C-strand subtelomeric region. The orchestrated action of the nucleoprotein assembly prevents telomeres from being recognized as DNA double-strand breaks, avoiding local DNA damage repair, and ensuring genome stability and cell proliferation. DNA replication of the genome is a complex process, prone to impediments and errors, mainly due to DNA lesions, secondary structure, and proteins bound to the DNA. Such problems may lead to the accumulation of chromosomal mutations and impair chromosome segregation, deleterious consequences for an organism. Genomic and telomeric DNA are also subject to potential genotoxic damages, even if they are not being replicated. Thus, cells developed different mechanisms to fix most of these DNA damages and preserve genome content for their offspring. The compilation of these mechanisms is called DNA repair.
Studies have been shedding light on these research questions for decades, but there are questions still unanswered. The elucidation of biochemical, molecular, and cellular mechanisms involving DNA and RNA metabolism remains one of the most important scientific challenges of our time. In this Research Topic, we aim to gather articles that encompass novel insights, as well as emerging methods, into DNA and RNA biology with a focus on:
- Replication origins licensing and firing;
- Replication fork dynamics;
- Factors associated with DNA replication;
- Repair processes associated with replication and telomere damage;
- Biogenesis of telomeric ncRNAs;
- Shelterinand other telomere-associated proteins;
- Telomerase dynamics and regulation;
- Telomere lengthening control;
- Homologous recombination repair (HR);
- Non-homologous end joining (NHEJ);
- Nucleotide excision repair (NER);
- Base excision repair (BER);
- Mismatch repair (MMR)
Original research manuscripts, brief reports, mini-reviews, and reviews will be welcome.
Keywords: DNA Replication, DNA Repair, Telomeres, Telomerase, Telomere-related RNAs
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.