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An Evolutionary Conserved DNA Replication Stress Response in Planarian
Author(s) -
Shamoon Ushna,
Tirgar Reyhaneh,
Akpati Lois,
Sawyer Nathaniel,
Nam Edward
Publication year - 2018
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.2018.32.1_supplement.lb548
Subject(s) - planarian , regeneration (biology) , microbiology and biotechnology , biology , dna replication , cell division , mitosis , genetics , dna , cell
S. mediterranea is a planarian with extensive regenerative ability which requires substantial cell division. Adult stem cells (SCs) divide many times over an organism's lifespan to renew tissues. The reduced capacity of adult SCs to regenerate old and damaged tissue results in aging. However, DNA replication stress occurs every cell division and must be resolved. From yeast to man, an evolutionary conserved DNA replication stress response (RSR) is essential for life. The RSR is a signal transduction pathway regulated by Ataxia‐telangiectasia and Rad3‐Related kinase (ATR) and Checkpoint 1 kinase (CHK1) to respond to replication stress. However, the RSR has not been established in planarian nor do we know if it functions in regeneration. We hypothesize that the RSR may be essential for regeneration. Preliminary results show reduced regenerative ability in the presence of hydroxyurea (HU), a replication stress inducing agent. However, low concentrations (2mM) did not attenuate regeneration, indicating that the RSR may be present and able to overcome replication stress. To test this, we treated amputated tails with HU, ATR inhibitor (ATRi), and a combination of both. In 2mM HU, tails regenerated similarly to control. We observed only a one day delay in regeneration with ATRi alone. However, ATRi and 2mM HU in combination prevented planarian regeneration completely. This synergistic effect suggests that ATR is significant in the response to replication stress during regeneration. To obtain genetic evidence, we are in the process of knocking down ATR as well as other RSR genes like CHK1, WRN, etc. Further determining the importance of RSR genes in planarian will elucidate the conserved components and allow us to understand how the RSR contributes to the incredible regenerative abilities in planarian. Support or Funding Information This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .