0000000000217268
AUTHOR
Holger Richly
Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans
Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4. Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of…
Autophagy during ageing – from Dr Jekyll to Mr Hyde
Autophagy is a ubiquitous catabolic process, which causes cellular bulk degradation through vesicular engulfment of obsolete, damaged or harmful cytoplasmic components. While autophagy regulates cellular homeostasis during development and in youth, there is mounting evidence that autophagy becomes increasingly dysfunctional with age. Recent work in Caenorhabditis elegans even suggests that late-life dysfunctional autophagy exhibits detrimental effects that drive the ageing process. Other studies link elevated autophagy closely to increased health and longevity. This review aims to put these apparently opposing views into perspective and define our current understanding of the role of autoph…
DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites
The endoribonuclease DICER facilitates chromatin decondensation during lesion recognition following UV exposure. Chitale and Richly show that DICER mediates the recruitment of the methyltransferase MMSET, which catalyzes the dimethylation of histone H4 at lysine 20 and facilitates the recruitment of the nucleotide excision repair factor XPA.
DICER and ZRF1 contribute to chromatin decondensation during nucleotide excision repair
Abstract Repair of damaged DNA relies on the recruitment of DNA repair factors in a well orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by chromatin remodelers to allow for binding of repair factors and for DNA repair to occur. Recent studies have implicated members of the SWI/SNF and INO80 families as well as PARP1 in nucleotide excision repair (NER). In this study, we report that the endonuclease DICER is implicated in chromatin decondensation during NER. In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner. The H2A–ubiquitin binding protein ZRF1 and DICER together impact on the chromatin conformation via PARP1. Moreover, …
Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans
AbstractAutophagy is a ubiquitous catabolic process, which causes cellular bulk degradation of cytoplasmic components and thereby regulates cellular homeostasis. Inactivation of autophagy has been linked with detrimental effects to cells and organisms. The antagonistic pleiotropy theory postulates that fitness promoting genes during youth are harmful during aging (Williams 1957). On this basis we examined genes mediating post-reproductive longevity using an RNA interference screen. From this screen we identified 30 novel regulators of post-reproductive longevity including pha-4. Through downstream analysis of pha-4 we identify that genes governing the early stages of autophagy up until the …