DNA double-strand breaks (DSBs) are cytotoxic DNA lesions that must be repaired as soon as possible because it can cause chromosomal aberrations and cell death. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are the pathways that mainly repair these ruptures. HR process is finely regulated by synchronized posttranslational modifications including phosphorylation, ubiquitylation, and SUMOylation. The ubiquitin (Ub) modifications at damaged chromatin serve as recruitment platforms for DSB repair complexes by facilitating binding sites or regulating the interaction between proteins. Thus, SUMOylation has been associated with protein interaction, enzymatic activity, and chromatin mobility. Several DNA damage factors have been found to be ubiquitylated and SUMOylated including histones (H2AX) and proteins such as Mre11, Rad51, NBS1, and BRCA1. Regarding ubiquitylation-mediated regulation of DNA repair, RNF168 and RNF8 E3 ligases have turned out to be a key step in DNA damage repair regulation. Interestingly, there is evidence that the Ub signaling mechanism is ancestral, and this emphasizes its importance.
Part of the book: Ubiquitination Governing DNA Repair
The mitochondrial genomic material (mtDNA), similarly to nuclear genome, is exposed to a plethora of exogenous and endogenous agents, as well as natural processes like replication that compromise the integrity and fidelity of the mtDNA, despite the abovementioned, the mtDNA does not contain genes involved in DNA repair, therefore mitochondria completely depend on the importation of nuclear-encoded elements to achieve genome maintenance, which implies a coordinated crosstalk between these two organelles. It has been determined that to counteract damage, mitochondria possess well-defined repair pathways quite similar to those of the nucleus, among which are: base excision repair (BER), mismatch repair (MMR), single-strand break repair (SSBR), microhomology-mediated end joining (MMEJ), and probably homology recombination dependent repair (HRR). If these repair pathways are nonfunctional and the lesions remain unrepaired, the emergence of mutations, deletions, and other insults may result in compromised cellular viability and disease.
Part of the book: DNA Repair