ABSTRACT
RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the homology-dependent repair of DNA damage for genomic stability. The formation of the RAD51 filament is promoted by various RAD51-interacting proteins including RAD51 paralogues. However, the mechanisms underlying the differential control of RAD51-filament dynamics by these factors remain largely unknown. Here, we report a role for the human RAD51 paralogue, SWSAP1, as a novel regulator of RAD51 assembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. The dismantling activity of FIGNL1 does not require its ATPase but depends on RAD51-binding. Purified SWSAP1 inhibits the RAD51-dismantling activity of FIGNL1. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.
Subject(s)
ATPases Associated with Diverse Cellular Activities/metabolism , Microtubule-Associated Proteins/metabolism , Nuclear Proteins/metabolism , Rad51 Recombinase/metabolism , Rec A Recombinases/physiology , Sequence Homology, Amino Acid , Amino Acid Motifs , Amino Acid Sequence , Animals , Cell Line , Chromosomes, Human/metabolism , DNA/metabolism , DNA Damage , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/metabolism , Germ Cells/metabolism , Humans , Mice, Inbred C57BL , Mice, Knockout , Mitosis , Models, Biological , Protein Binding , Rec A Recombinases/geneticsABSTRACT
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and hyperactivity/impulsivity, and is often treated pharmacologically. It is necessary to use both subjective and objective assessments to diagnose and determine the efficacy of pharmacological treatment in children with ADHD, but cognitive assessment tools for ADHD are scarce. We examined a computer-administered, brief, and repeatable cognitive assessment tool: CogHealth. The aims of this study were to use the CogHealth battery, an objective assessment tool, to compare cognitive function between children with ADHD or ADHD + autism spectrum disorder (ASD) and healthy children and to assess improvements in cognitive function following pharmacological treatment. METHODS: We measured the cognitive function of nine children with ADHD or ADHD + ASD using CogHealth and compared the results with those of 33 age-matched children from the community. Cognitive function comparisons were made before and after psychostimulant treatment with methylphenidate. RESULTS: We detected significant cognitive abnormalities in the children with ADHD, compared with the control subjects. The children with pre-treatment ADHD had significantly more errors on the detection task (DT), and more anticipatory errors in the one card learning task, compared with control children. The children with ADHD significantly improved their accuracy on the one back test (OBT), and had significantly fewer errors, anticipatory errors, and shorter reaction times after osmotic-release oral system methylphenidate treatment. CONCLUSION: The DT is a useful neurocognitive function assessment for children with ADHD, and the OBT can measure pharmacological treatment effectiveness in children with ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Central Nervous System Stimulants/therapeutic use , Cognition/drug effects , Methylphenidate/therapeutic use , Neuropsychological Tests , Attention Deficit Disorder with Hyperactivity/drug therapy , Child , Cognition/physiology , Female , Humans , Male , Predictive Value of Tests , ROC Curve , Treatment OutcomeABSTRACT
BACKGROUND: Autism spectrum disorders (ASD) are characterized by persistent deficits in social communication and social interaction across contexts, and are associated with restricted patterns of behavior. The developmental quotient (DQ) is based on the developmental age and chronological age of children. This study investigated the utility of the DQ to estimate cognitive ability in young children with ASD. METHODS: The DQ and intelligence quotient (IQ) were assessed using the Kyoto Scale of Psychological Development 2001 (KSPD) and Wechsler Intelligence Scale for Children-III (WISC-III), respectively. The correlation between the DQ and IQ was then analyzed among children with ASD. RESULTS: We enrolled 18 children with ASD (16 boys, two girls; age, 63.6 ± 9.4 months; age range, 45-83 months). Overall, Cognitive-Adaptive and Language-Social DQ scores were significantly correlated with IQ score in the full scale, verbal, and performance domains. Full-scale IQ and overall DQ had a linear correlation (y = -22.747 + 1.177x, R2 = 0.677, R = 0.823). CONCLUSIONS: The DQ scores obtained using the KSPD were a reasonable estimate of cognitive ability in children with ASD. The KSPD may be a useful alternative to the WISC-III for young children with ASD and could facilitate earlier assessment.
