Warner HR (2005) Mechanisms of Ageing & Development "Longevity genes: from primitive organisms to humans."

Warner HR

[Mechanisms of Ageing & Development, 2005]

Recent results indicate that the longevity of both invertebrates and vertebrates can be altered through genetic manipulation and pharmacological intervention. Most of these interventions involve alterations of one or more of the following: insulin/IGF-I signaling pathway, caloric intake, stress resistance and nuclear structure. How longevity regulation relates to aging per se is less clear, but longevity increases are usually accompanied by extended periods of good health. How these results will translate to primate aging and longevity remains to be shown.

Adelman CA et al. (2010) FEBS Lett "Metabolism of postsynaptic recombination intermediates."

Boulton SJ, Adelman CA

[FEBS Lett, 2010]

DNA double strand breaks and blocked or collapsed DNA replication forks are potentially genotoxic lesions that can result in deletions, aneuploidy or cell death. Homologous recombination (HR) is an essential process employed during repair of these forms of damage. HR allows for accurate restoration of the damaged DNA through use of a homologous template for repair. Although inroads have been made towards understanding the mechanisms of HR, ambiguity still surrounds aspects of the process. Until recently, relatively little was known concerning metabolism of postsynaptic RAD51 filaments or how synthesis dependent strand annealing intermediates are processed. This review discusses recent findings implicating RTEL1, HELQ and the Caenorhabditis elegans RAD51 paralog RFS-1 in post-strand exchange events during HR.

Belan O et al. (2021) Curr Opin Genet Dev "Mechanism of mitotic recombination: insights from C. elegans."

Boulton SJ, Anand R, Belan O

[Curr Opin Genet Dev, 2021]

Homologous recombination (HR) plays a critical role in largely error-free repair of mitotic and meiotic DNA double-strand breaks (DSBs). DSBs are one of the most deleterious DNA lesions, which are repaired by non-homologous end joining (NHEJ), homologous recombination (HR) or, if compromised, micro-homology mediated end joining (MMEJ). If left unrepaired, DSBs can lead to cell death or if repaired incorrectly can result in chromosome rearrangements that drive cancer development. Here, we describe recent advances in the field of mitotic HR made using Caenorhabditis elegans roundworm, as a model system.

van Kregten M et al. (2014) Exp Cell Res "The repair of G-quadruplex-induced DNA damage."

Tijsterman M, van Kregten M

[Exp Cell Res, 2014]

G4 DNA motifs, which can form stable secondary structures called G-quadruplexes, are ubiquitous in eukaryotic genomes, and have been shown to cause genomic instability. Specialized helicases that unwind G-quadruplexes in vitro have been identified, and they have been shown to prevent genetic instability in vivo. In the absence of these helicases, G-quadruplexes can persist and cause replication fork stalling and collapse. Translesion synthesis (TLS) and homologous recombination (HR) have been proposed to play a role in the repair of this damage, but recently it was found in the nematode Caenorhabditis elegans that G4-induced genome alterations are generated by an error-prone repair mechanism that is dependent on the A-family polymerase Theta (Pol ). Current data point towards a scenario where DNA replication blocked at G-quadruplexes causes DNA double strand breaks (DSBs), and where the choice of repair pathway that can act on these breaks dictates the nature of genomic alterations that are observed in various organisms.