title: Meier-Gorlin syndrome and Wolf-Hirschhorn syndrome: two developmental disorders highlighting the importance of efficient DNA replication for normal development and neurogenesis.
abstract: Microcephaly represents one of the most obvious clinical manifestations of impaired neurogenesis. Defects in the DNA damage response, in DNA repair, and structural abnormalities in centrosomes, centrioles and the spindle microtubule network have all been demonstrated to cause microcephaly in humans. Work describing novel functional defects in cell lines from individuals with either Meier-Gorlin syndrome or Wolf-Hirschhorn syndrome highlight the significance of optimal DNA replication and S phase progression for normal human development, including neurogenesis. These findings illustrate how different primary defects in processes impacting upon DNA replication potentially influence similar phenotypic outcomes, including growth retardation and microcephaly. Herein, we will describe the nature of the S phase defects uncovered for each of these conditions and highlight some of the overlapping cellular features.
authors.affiliation: Human DNA Damage Response Disorders Group, Genome Damage & Stability Centre, University of Sussex, Brighton, East Sussex BN1 9RQ, United Kingdom.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kerzendorfer
authors.forename: Rita
authors.initials: R
authors.lastname: Colnaghi
authors.forename: Iga
authors.initials: I
authors.lastname: Abramowicz
authors.forename: Gillian
authors.initials: G
authors.lastname: Carpenter
authors.forename: Mark
authors.initials: M
authors.lastname: O'Driscoll
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002502:Centrioles / Q000235:genetics / Q000473:pathology; D018385:Centrosome / Q000473:pathology; D065817:Congenital Microtia; D004261:DNA Replication; D002658:Developmental Disabilities / Q000235:genetics; D004195:Disease Models, Animal; D004423:Ear / Q000002:abnormalities*; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D008844:Micrognathism / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics*; D010329:Patella / Q000002:abnormalities*; D054877:Wolf-Hirschhorn Syndrome / Q000235:genetics*
keywords: DNA replication; Dormant origins; Microcephaly; Nucleosome assembly; Origin licensing