No abstract

The study demonstrated great promise in creating a health-conducive environment that positively impacts weight and gross motor skill development in children at risk for obesity. Program efficacy should be tested in a randomized trial.

Lysine methylation is a common posttranslational modification (PTM) of histones that is important for the epigenetic regulation of transcription and chromatin in eukaryotes. Increasing evidence demonstrates that in addition to histones, lysine methylation also occurs on various non-histone proteins, especially transcription- and chromatin-regulating proteins. In this review, we will briefly describe the histone lysine methyltransferases (KMTs) that have a broad spectrum of non-histone substrates. We will use p53 and nuclear receptors, especially estrogen receptor alpha, as examples to discuss the dynamic nature of non-histone protein lysine methylation, the writers, erasers, and readers of these modifications, and the crosstalk between lysine methylation and other PTMs in regulating the functions of the modified proteins. Understanding the roles of lysine methylation in normal cells and during development will shed light on the complex biology of diseases associated with the dysregulation of lysine methylation on both histones and non-histone proteins.

Summary We identified UHRF1 as a binding factor for DNA interstrand crosslink (ICL) lesions through affinity purification of ICL-recognition activities. UHRF1 is recruited to DNA lesions in vivo and binds directly to ICL-containing DNA. UHRF1-deficient cells display increased sensitivity to a variety of DNA damages. We found that loss of UHRF1 led to retarded lesion processing and reduced recruitment of ICL repair nucleases to the site of DNA damage. UHRF1 interacts physically with both ERCC1 and MUS81, two nucleases involved in the repair of ICL lesions. Depletion of both UHRF1 and components of the Fanconi anemia pathway resulted in increased DNA damage sensitivity compared to defect of each mechanism alone. These results suggest that UHRF1 promotes recruitment of lesion-processing activities via its DNA damage recognition affinity and functions as a nuclease recruitment scaffold in parallel to the Fanconi anemia pathway.

SUMMARY The Fanconi Anemia (FA) core complex provides the essential E3 ligase function for the FA pathway activation through the spatially defined FANCD2 ubiquitination. Of the seven FA gene products forming the core complex, FANCL possesses a RING domain with demonstrated E3 ligase activity. The other six components have no clearly defined roles. Through epistatic analyses, we identified three functional modules in the FA core complex: a catalytic module consisting of FANCL, FANCB, and FAAP100 is absolutely required for the E3 ligase function; the FANCA-FANCG-FAAP20 module and the FANCC-FANCE-FANCF module provide non-redundant and ancillary functions supporting the chromatin and DNA damage association of the catalytic module. Disruption of the catalytic module renders total loss of the core complex function whereas loss of any ancillary module component does not. Our work revealed the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex.