Mouse Slfn8 and Slfn9 genes complement human cells lacking SLFN11 during the replication stress response.

The Schlafen (SLFN)11 gene has been implicated in various biological processes such as suppression of HIV replication, replication stress response, and sensitization of cancer cells to chemotherapy. Due to the rapid diversification of the SLFN family members, it remains uncertain whether a direct ortholog of human SLFN11 exists in mice. Here we show that mSLFN8/9 and hSLFN11 were rapidly recruited to microlaser-irradiated DNA damage tracks.

RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair.

SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown.

SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells.

Fanconi anemia (FA) is a hereditary disorder caused by mutations in any 1 of 22 FA genes. The disease is characterized by hypersensitivity to interstrand crosslink (ICL) inducers such as mitomycin C (MMC). In addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication forks from nucleolytic degradation during replication stress, which may have a profound impact on FA pathophysiology.

USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA-RNA helicase DHX9.

The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related nuclear speckle factors as potential HR regulators. Among the top hits, we provide evidence showing that USP42, which is a hitherto unidentified nuclear speckles protein, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection.

Open-capsule intraocular lens to prevent posterior capsule opacification.

Purpose: To develop a single-piece open-capsule intraocular lens (IOL) that can be inserted through a small incision and that prevents posterior capsule opacification (PCO) by expanding the capsule and circulating aqueous humor into the capsular bag.

Setting: Department of Ophthalmology, Dokkyo Medical University, Tochigi, Japan.

Design: Experimental study.

RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.

RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3.

FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end.

The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament.

Defects in homologous recombination repair behind the human diseases: FA and HBOC.

Hereditary breast and ovarian cancer (HBOC) syndrome and a rare childhood disorder Fanconi anemia (FA) are caused by homologous recombination (HR) defects, and some of the causative genes overlap. Recent studies in this field have led to the exciting development of PARP inhibitors as novel cancer therapeutics and have clarified important mechanisms underlying genome instability and tumor suppression in HR-defective disorders. In this review, we provide an overview of the basic molecular mechanisms governing HR and DNA crosslink repair, highlighting BRCA2, and the intriguing relationship between HBOC and FA.

Decreased visual acuity resulting from glistening and sub-surface nano-glistening formation in intraocular lenses: A retrospective analysis of 5 cases.

Background: To report on five patients with decreased visual acuity due to glistening and severe sub-surface nano-glistening (SSNG) formation within their intraocular lenses (IOLs).

Design: Case reports and analysis of extracted IOLs.

Participants And Samples: We report improved visual acuity when IOLs with severe glistening and SSNG were exchanged for clear IOLs in five patients.

SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells.

Recent studies have shown that homologous recombination (HR) requires chromatin repression as well as relaxation at DNA double strand breaks (DSBs). HP1 and SUV39H1/2 are repressive factors essential for HR. Here, we identify SETDB1 as an additional compacting factor promoting HR.

Influence of intraocular lens implantation on anterior capsule contraction and posterior capsule opacification.

Purpose: To evaluate whether and how intraocular lens (IOL) implantation influences the development of anterior capsule contraction and posterior capsule opacification (PCO).

Setting: Department of Ophthalmology, Dokkyo Medical University, Mibu, Tochigi, Japan.

Design: Experimental study.

Co-operation of BRCA1 and POH1 relieves the barriers posed by 53BP1 and RAP80 to resection.

In G2 phase cells, DNA double-strand break repair switches from DNA non-homologous end-joining to homologous recombination. This switch demands the promotion of resection. We examine the changes in 53BP1 and RAP80 ionizing radiation induced foci (IRIF) in G2 phase, as these are factors that restrict resection.

Japanese mothers' breastfeeding knowledge and attitudes assessed by the Iowa Infant Feeding Attitudes Scale.

This study describes Japanese mothers' knowledge and attitudes towards breastfeeding using the Iowa Infant Feeding Attitudes Scale (IIFAS). A cross-sectional survey of 1,612 mothers was conducted in Japan in 2007. The participants were recruited at the free health checks conducted for infants at 18 months of age.

[Development of a new method to estimate patient surface dose distributions in IVR].

Recently, the angiography system used for interventional radiology (IVR) provides a device for measuring dose-area product (DAP), which is compulsory in European countries. The usefulness of DAP is that one can observe patient dose in real time during IVR and can obtain an integral dose by overall IVR procedure without a dosimeter directly placed on a patient. It is important to know the most irradiated region (hot spot) of the patient's skin and its maximum value in the dose management of IVR, but this information cannot be obtained only in DAP.

Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes.

Aneuploidy has been implicated as an important step leading to various neoplasias. Although genetic factors that block aneuploidy have been the subject of intense interest, the impact of pharmacological and environmental substances on the development of aneuploidy has not been studied. Here, we show that caffeine induces aneuploidy through asymmetrical cell division.

Preventing secondary cataract and anterior capsule contraction by modification of intraocular lenses.

Advances in intraocular lens (IOL) design have led to the use of lenses with improved performance including tinting, asphericity, multifocality and accommodation. To maximize the visual performance of these IOLs, postoperative complications such as secondary cataracts and anterior capsule contraction must be prevented. Various types of secondary cataracts may occur, each associated with complex biological reactions.

Early G2/M checkpoint failure as a molecular mechanism underlying etoposide-induced chromosomal aberrations.

Topoisomerase II (Topo II) inhibitors are cell cycle-specific DNA-damaging agents and often correlate with secondary leukemia with chromosomal translocations involving the mixed-lineage leukemia/myeloid lymphoid leukemia (MLL) gene on chromosome 11 band q23 (11q23). In spite of the clinical importance, the molecular mechanism for this chromosomal translocation has yet to be elucidated. In this study, we employed 2-color FISH and detected intracellular chromosomal translocations induced by etoposide treatment.

Detection of ATM gene mutation in human glioma cell line M059J by a rapid frameshift/stop codon assay in yeast.

A yeast-based frameshift/stop codon assay for examining ATM (ataxia telangiectasia mutated) mutations was established. Each of six fragments of a PCR-amplified coding sequence for ATM is inserted in frame by homologous recombination into a yeast URA3 fusion protein gene, and the transformants are assayed for growth in the absence of uracil. The usefulness of this assay was verified in a panel of cell lines derived from individuals with homozygous and heterozygous ATM mutations.