DNA damage responses by human ELGI in S phase are important to maintain genomic integrity Journal Article
| Authors: | Sikdar, N.; Banerjee, S.; Lee, K. Y.; Wincovitch, S.; Pak, E.; Nakanishi, K.; Jasin, M.; Dutra, A.; Myung, K. |
| Article Title: | DNA damage responses by human ELGI 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 ElgI plays an important role in S phase to preserve genomic stability. The level of ELGI is induced during recovery from a variety of DNA damage. In response to DNA damage, ELGI forms distinct foci at stalled DNA replication forks that are different from DNA double strand break foci. Targeted gene knockdown of ELGI resulted in spontaneous foci formation of γ-H2AX, 53BPI 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 ELGI by targeted gene knockdown. Knockdown of ELGI 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 ELGI was silenced by shRNA. Taken together, we propose that ELGI would be a new member of proteins involved in maintenance of genomic integrity. © 2009 Landes Bioscience. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; dna-binding proteins; dna replication; dna damage; homologous recombination; cell cycle s phase; cell protein; small interfering rna; rna, small interfering; rna interference; cell line, tumor; genomic instability; nucleotide sequence; atm protein; dna breaks, double-stranded; chromosome breakage; double stranded dna break; upregulation; gene silencing; histone h2ax; s phase; elg1; genome stability; rfc; gamma histone h2ax; protein elg1 |
| Journal Title: | Cell Cycle |
| Volume: | 8 |
| Issue: | 19 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2009-10-01 |
| Start Page: | 3199 |
| End Page: | 3207 |
| Language: | English |
| PUBMED: | 19755857 |
| PROVIDER: | scopus |
| PMCID: | PMC2880862 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "Source: Scopus" |
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