Novel regulatory mechanisms of mutagenic translesion DNA synthesis : characterization of REV1 in Saccharomyces cerevisiae

Cells are constantly subjected to DNA damage from endogenous and exogenous sources. Spontaneous DNA damage alone accounts for -30,000 DNA lesions per day in a mammalian cell. Cells are also exposed to an enormous variety of environmental agents that can cause a wide range of modified bases and aberrant DNA structures. To respond to the large diversity of DNA lesions that can be produced, cells possess a host of DNA repair and damage tolerance systems. The majority of these processes operate with exquisite accuracy to restore the correct DNA sequence and structure to maintain genomic stability. However, in some cases, DNA damage induces a mutagenic response and these mechanisms are responsible for the active introduction of mutations into the genomes of all organisms. Since the discovery in 1999 of a novel superfamily of error-prone translesion DNA polymerases, we have gained substantial insight into the biochemical mechanisms of DNA damage tolerance and mutagenesis. Translesion polymerases are specialized to insert a nucleotide opposite to DNA lesions and often produce mutations during the replication of undamaged DNA. It is now appreciated that the regulation of DNA damage tolerance systems at multiple levels is critical to the appropriate deployment of these potentially mutagenic translesion polymerases to prevent rampant mutagenesis.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Waters, Lauren S. (Lauren Stacey)

Advisor dc:contributor.advisor

• Graham C. Walker.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38629

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38629