title: The DNA damage response molecule MCPH1 in brain development and beyond.
abstract: Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly. In addition to its role in neurogenesis, MCPH1 plays a role in gonad development. MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models. Here, we review the role of MCPH1 in DNA damage response, cell cycle control, chromosome condensation and chromatin remodeling. We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies, including infertility and cancer.
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany Faculty of Biology and Pharmacy, Friedrich-Schiller University of Jena, Jena, Germany zhao-qi.wang@leibniz-fli.de.
authors.forename: Zhao-Qi
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D063646:Carcinogenesis; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins; D004249:DNA Damage; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; C547654:MCPH1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: DNA damage response; MCPH1; cell cycle; microcephaly; neurogenesis