THE ROLE OF TRANSLESION SYNTHESIS POLYMERASES REV1 AND POL η IN DNA DAMAGE RESPONSE

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McLeod, M. (2016). THE ROLE OF TRANSLESION SYNTHESIS POLYMERASES REV1 AND POL η IN DNA DAMAGE RESPONSE. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Our cells endure continuous challenges from byproducts of endogenous metabolic processes as well as outside sources such as UV light and environmental polltants. The DNA Damage Response (DDR) helps organisms cope with damage and coordinate an appropriate response pathway. It involves the initial detection of DNA damage and subsequent activation of the appropriate repair pathway, coordination of cell cycle progression, transcription activation, or activation of apoptosis or cellular senescence. ATR-Chk1 is one of the most studied DDR pathways and controls progression through the S-phase of the cell cycle. The translesion synthesis (TLS) pathway, once believed to act independently of the DDR pathways, ensures bypass of a DNA lesion in a rapid and often error-prone fashion. However, it remains largely unknown the interplay between the DDR and TLS pathways. In this research, we investigated the roles of two TLS polymerases, REV1 and Polη, to determine their function in the ATR-Chk1 pathway. Our data suggest that REV1 is important for the activation of ATR-Chk1 DDR pathway in response to interstand crosslinks and stalled replication forks, but is dispensable for the recruitment of checkpoint protein complex onto DNA damage sites or stalled forks. In addition, Polη is important for Chk1 phosphorylation in response to oxidative stress but not DNA replication stress. This research will help to understand how the TLS polymerases contribute to the DDR pathway to maintain genomic stability. Thus, our findings from this study will provide insight into how cells respond to chemotherapy drugs and environmental agents, and ultimately lead to new potential drug targeting mechanisms.

Details
Author

McLeod, Melissa

Title

THE ROLE OF TRANSLESION SYNTHESIS POLYMERASES REV1 AND POL η IN DNA DAMAGE RESPONSE

Physical Description

1 online resource (67 pages) : PDF

Date

2016

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Our cells endure continuous challenges from byproducts of endogenous metabolic processes as well as outside sources such as UV light and environmental polltants. The DNA Damage Response (DDR) helps organisms cope with damage and coordinate an appropriate response pathway. It involves the initial detection of DNA damage and subsequent activation of the appropriate repair pathway, coordination of cell cycle progression, transcription activation, or activation of apoptosis or cellular senescence. ATR-Chk1 is one of the most studied DDR pathways and controls progression through the S-phase of the cell cycle. The translesion synthesis (TLS) pathway, once believed to act independently of the DDR pathways, ensures bypass of a DNA lesion in a rapid and often error-prone fashion. However, it remains largely unknown the interplay between the DDR and TLS pathways. In this research, we investigated the roles of two TLS polymerases, REV1 and Polη, to determine their function in the ATR-Chk1 pathway. Our data suggest that REV1 is important for the activation of ATR-Chk1 DDR pathway in response to interstand crosslinks and stalled replication forks, but is dispensable for the recruitment of checkpoint protein complex onto DNA damage sites or stalled forks. In addition, Polη is important for Chk1 phosphorylation in response to oxidative stress but not DNA replication stress. This research will help to understand how the TLS polymerases contribute to the DDR pathway to maintain genomic stability. Thus, our findings from this study will provide insight into how cells respond to chemotherapy drugs and environmental agents, and ultimately lead to new potential drug targeting mechanisms.

Genre

masters theses

Subjects--Topics

Molecular biology
Biology
Cytology

Degree

M.S.

Keywords

Dna Damage Response
Pol Eta
Rev1
Translesion Synthesis

Subject Area

Biology

Advisor(s)

Yan, Shan

Committee Members

Dreau, Didier
Reitzel, Adam

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2016.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

McLeod_uncc_0694N_11300

Permalink

http://hdl.handle.net/20.500.13093/etd:752