CDK2 phosphorylation of Werner protein (WRN) contributes to WRN's DNA double-strand break repair pathway choice.

Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability, which is caused by WRN protein deficiency. WRN participates in DNA metabolism including DNA repair. In a previous report, we showed that WRN protein is recruited to laser-induced DNA double-strand break (DSB) sites during various stages of the cell cycle with similar intensities, supporting that WRN participates in both non-homologous end joining (NHEJ) and homologous recombination (HR).

Author Correction: Rev1 contributes to proper mitochondrial function via the PARP-NAD-SIRT1-PGC1α axis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB hippocampus, but not in CSB cortex or WT brain.

Rev1 contributes to proper mitochondrial function via the PARP-NAD-SIRT1-PGC1α axis.

Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress.

Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions.

Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize aging. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions and how these ultimately affect the physiology of cells and tissues.