Yeast RAD2, a homolog of human XPG, plays a key role in the regulation of the cell cycle and actin dynamics

Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma pigmentosum (XP). Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been cl...

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Bibliographic Details
Published in:Biology open 2014-01, Vol.3 (1), p.29-41
Main Authors: Kang, Mi-Sun, Yu, Sung-Lim, Kim, Ho-Yeol, Gorospe, Choco Michael, Choi, Byung Hyune, Lee, Sung Haeng, Lee, Sung-Keun
Format: Article
Language:English
Subjects:
Actin
Actin dynamics
Amino acids
Assembly
Cell cycle
Cockayne syndrome
Defects
DNA damage
Gene deletion
Irradiation
Life span
Mutation
Polarization
RAD2
Stalling
Transcription
Ultraviolet radiation
Xeroderma pigmentosum
Yeasts
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Summary:Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma pigmentosum (XP). Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been clearly demonstrated. Here, we provide evidence for the involvement of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell growth arrest, the cell cycle stalling, a defective α-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was sufficient to induce hyper-cell polarization. In addition, RAD2 genetically interacts with TPM1 during cell polarization. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.20136403