Stephanie Smith1, Ji‐Young Hwang2, Soma Banerjee2, Anju Majeed2, Amitabha Gupta2, Kyungjaem Myung2
1Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892 USA
2Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892
Tóm tắt
Different types of gross chromosomal rearrangements (GCRs), including translocations, interstitial deletions, terminal deletions with
de novo
telomere additions, and chromosome fusions, are observed in many cancers. Multiple pathways, such as S-phase checkpoints, DNA replication, recombination, chromatin remodeling, and telomere maintenance that suppress GCRs have been identified. To experimentally expand our knowledge of other pathway(s) that suppress GCRs, we developed a generally applicable genome-wide screening method. In this screen, we identified 10 genes (
ALO1, CDC50, CSM2, ELG1, ESC1, MMS4, RAD5, RAD18, TSA1
, and
UFO1
) that encode proteins functioning in the suppression of GCRs. Moreover, the breakpoint junctions of GCRs from these GCR mutator mutants were determined with modified breakpoint-mapping methods. We also identified nine genes (
AKR1, BFR1, HTZ1, IES6, NPL6, RPL13B, RPL27A, RPL35A
, and
SHU2
) whose mutations generated growth defects with the
pif1
Δ mutation. In addition, we found that some of these mutations changed the telomere size.
