title: The Hus1 homologue of Leishmania major encodes a nuclear protein that participates in DNA damage response.
abstract: The protozoan parasite Leishmania presents a dynamic and plastic genome in which gene amplification and chromosome translocations are common phenomena. Such plasticity hints at the necessity of dependable genome maintenance pathways. Eukaryotic cells have evolved checkpoint control systems that recognize altered DNA structures and halt cell cycle progression allowing DNA repair to take place. In these cells, the PCNA-related heterotrimeric complex formed by the proteins Hus1, Rad9, and Rad1 is known to participate in the early steps of replicative stress sensing and signaling. Here we show that the Hus1 homolog of Leishmania major is a nuclear protein that improves the cell capability to cope with replicative stress. Overexpression of LmHus1 confers resistance to the genotoxic drugs hydroxyurea (HU) and methyl methanesulfonate (MMS) and resistance to HU correlates to reduced net DNA damage upon LmHus1 expression.
authors.affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Vinicius S
authors.initials: VS
authors.lastname: Nunes
authors.forename: Jeziel D
authors.initials: JD
authors.lastname: Damasceno
authors.forename: Raimundo
authors.initials: R
authors.lastname: Freire
authors.forename: Luiz R O
authors.initials: LR
authors.lastname: Tosi
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D018320:Leishmania major / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology; D008969:Molecular Sequence Data; D009153:Mutagens / Q000633:toxicity; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D009153:Mutagens; D009687:Nuclear Proteins; D015800:Protozoan Proteins