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How Replication Stress Drives Genome Instability
Author(s) -
Forsburg Susan
Publication year - 2019
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.2019.33.1_supplement.345.4
Subject(s) - dna re replication , control of chromosome duplication , biology , dna replication , mitosis , genetics , genome instability , origin recognition complex , dna damage , microbiology and biotechnology , dna repair , cell cycle , cell cycle checkpoint , pre replication complex , chromothripsis , chromosome segregation , eukaryotic dna replication , chromosome , dna , gene
DNA replication stress can result from intrinsic challenges (such as defective replication proteins, collisions with transcription machinery, or synthesis through repetitive sequences), or extrinsic agents (such as agents that damage DNA (UV, MMS, CPT) or starve for nucleotides (HU)). The cell deploys a variety of checkpoint and repair proteins to manage accumulation of single stranded DNA, replication fork stalling, fork regression and recombination intermediates to repair. Increasingly, it is clear that the response to stress is not just important for completion of S phase, but impacts mitosis and faithful chromosome segregation. Thus, response to replication stress is an initial barrier to malignant transformation. Our study employs a model genetic system, the fission yeast S. pombe . We are using mutations that attenuate core components of the replication machinery or epigenetic components, to investigate different kinds of stress and how they engage, or evade, the normal cellular response. Our approach is grounded in analysis of the intact cell and determining the consequences of replication stress including mutation, chromosome mis‐segregation, or gross chromosome rearrangements and translocation. A key component is monitoring stress responders in real time using dynamic live cell imaging. Recent studies have focused on how checkpoint evasion leads to ongoing mitosis and chromosome rearrangement, and on how the response of cells in the meiotic pathway differs from the vegetative cell cycle. Current investigations will be discussed. Support or Funding Information NIH R35 GM118109 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .