Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability
نویسندگان
چکیده
منابع مشابه
Translesion synthesis of acetylaminofluorene-dG adducts by DNA polymerase zeta is stimulated by yeast Rev1 protein.
Translesion synthesis is an important mechanism in response to unrepaired DNA lesions during replication. The DNA polymerase zeta (Polzeta) mutagenesis pathway is a major error-prone translesion synthesis mechanism requiring Polzeta and Rev1. In addition to its dCMP transferase, a non-catalytic function of Rev1 is suspected in cellular response to certain types of DNA lesions. However, it is no...
متن کاملInteraction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis.
Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first step, a Y-family TLS enzyme, typically Polη, Polι, or Polκ, inserts a nucleotide ...
متن کاملProteasomal regulation of the mutagenic translesion DNA polymerase, Saccharomyces cerevisiae Rev1.
Translesion DNA synthesis (TLS) functions as a tolerance mechanism for DNA damage at a potentially mutagenic cost. Three TLS polymerases (Pols) function to bypass DNA damage in Saccharomyces cerevisiae: Rev1, Pol ζ, a heterodimer of the Rev3 and Rev7 proteins, and Pol η (Rad30). Our lab has shown that S. cerevisiae Rev1 protein levels are under striking cell cycle regulation, being ∼50-fold hig...
متن کاملCharacterization of a coupled DNA replication and translesion synthesis polymerase supraholoenzyme from archaea
The ability of the replisome to seamlessly coordinate both high fidelity and translesion DNA synthesis requires a means to regulate recruitment and binding of enzymes from solution. Co-occupancy of multiple DNA polymerases within the replisome has been observed primarily in bacteria and is regulated by posttranslational modifications in eukaryotes, and both cases are coordinated by the processi...
متن کاملREV1 restrains DNA polymerase ζ to ensure frame fidelity during translesion synthesis of UV photoproducts in vivo
Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (6-4) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand the mechanisms and control of lesion byp...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Science Advances
سال: 2020
ISSN: 2375-2548
DOI: 10.1126/sciadv.aaz7808