DNA damage repair proteins across the Tree of Life.

Genome maintenance is orchestrated by a highly regulated DNA damage response with specific DNA repair pathways. Here, we investigate the phylogenetic diversity in the recognition and repair of three well-established DNA lesions, primarily repaired by base excision repair (BER) and ribonucleotide excision repair (RER): (1) 8-oxoguanine, (2) abasic site, and (3) incorporated ribonucleotide in DNA in 11 species: and Using quantitative mass spectrometry, we identified 337 binding proteins across these species. Of these proteins, 99 were previously characterized to be involved in DNA repair.

Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase.

Single ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free rNMP removal. In some pathological conditions, rNMP removal is impaired.

Checkpoint adaptation in recombination-deficient cells drives aneuploidy and resistance to genotoxic agents.

Human cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ recombination-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge.

Non-coding RNAs at the Eukaryotic rDNA Locus: RNA-DNA Hybrids and Beyond.

The human ribosomal DNA (rDNA) locus encodes a variety of long non-coding RNAs (lncRNAs). Among them, the canonical ribosomal RNAs that are the catalytic components of the ribosomes, as well as regulatory lncRNAs including promoter-associated RNAs (pRNA), stress-induced promoter and pre-rRNA antisense RNAs (PAPAS), and different intergenic spacer derived lncRNA species (IGSRNA). In addition, externally encoded lncRNAs are imported into the nucleolus, which orchestrate the complex regulation of the nucleolar state in normal and stress conditions via a plethora of molecular mechanisms.