title: DNA damage responses by human ELG1 in S phase are important to maintain genomic integrity.
abstract: Genomic integrity depends on DNA replication, recombination and repair, particularly in S phase. We demonstrate that a human homologue of yeast Elg1 plays an important role in S phase to preserve genomic stability. The level of ELG1 is induced during recovery from a variety of DNA damage. In response to DNA damage, ELG1 forms distinct foci at stalled DNA replication forks that are different from DNA double strand break foci. Targeted gene knockdown of ELG1 resulted in spontaneous foci formation of gamma-H2AX, 53BP1 and phosphorylated-ATM that mark chromosomal breaks. Abnormal chromosomes including fusions, inversions and hypersensitivity to DNA damaging agents were also observed in cells expressing low level of ELG1 by targeted gene knockdown. Knockdown of ELG1 by siRNA reduced homologous recombination frequency in the I-SceI induced double strand break-dependent assay. In contrast, spontaneous homologous recombination frequency and sister chromatin exchange rate were upregulated when ELG1 was silenced by shRNA. Taken together, we propose that ELG1 would be a new member of proteins involved in maintenance of genomic integrity.
authors.affiliation: Genome Instability Section, Genetics and Molecular Biology Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nilabja
authors.initials: N
authors.lastname: Sikdar
authors.forename: Soma
authors.initials: S
authors.lastname: Banerjee
authors.forename: Kyoo-young
authors.initials: KY
authors.lastname: Lee
authors.forename: Stephen
authors.initials: S
authors.lastname: Wincovitch
authors.forename: Evgenia
authors.initials: E
authors.lastname: Pak
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Amalia
authors.initials: A
authors.lastname: Dutra
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase
chemical_list: C546328:ATAD5 protein, human; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities