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Elg1 (Enhanced level of genome instability 1) has an essential role in early development and suppressing tumorigenesis
Author(s) -
Sikdar Nilabja,
Myung Kyungjae
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.874.3
Subject(s) - genome instability , biology , chromosome instability , genetics , dna re replication , dna replication , carcinogenesis , dna repair , dna damage , chromosome , gene , eukaryotic dna replication , dna
High levels of chromosome rearrangements known as gross chromosomal rearrangements (GCRs) such as translocations, deletion of chromosome arm, interstitial deletions, inversions and gene amplification, have been reported in many cancers. Multiple pathways, such as S‐phase checkpoints, DNA replication, chromatin remodeling, and telomere maintenance suppress the GCR formation. Elg1 was discovered during the genome wide screening of yeast S. cerevisiae as a suppressor of GCR formation. Elg1 is a suppressor of genomic instability and functions in DNA repair in yeast and human. Objectives To investigate whether the loss of Elg1 in mouse a in vivo model system causes any genomic disorder and null Elg1 MEF cells shows any Genomic instability phenotypes. Results Absence of Elg1 in mice caused early embryonic lethality and zebra fish Elg1 MO embryos also has developmental problem suggesting Elg1 has an essential role during early development. This embryonic developmental defect rescued in absence of p53 in zebrafish and developed normal. The heterozygous mice developed tumors including sarcoma, carcinoma, and adenoma in various organs from 11 month after birth. The Elg1 +/m MEFs and Elg1 +/− chicken DT 40 cells show high level of DN A damage sensitivity as well as chromosomal instability in respond to DNA damage. High levels of genomic rearrangements were observed in tumors developed in the Elg1 +/m mice by comparative genome hybridization. The microarray and pathway analysis of tumors from the Elg1 heterozygous mice showed the upregulation of Smad independent Tgf‐β pathway. Conclusions Taken together, Elg1 has an essential role in early development that appears to have a close link to suppress genomic instability and ultimately tumorigenesis.