Small-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1 interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance
نویسندگان
چکیده
منابع مشابه
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.
Translesion synthesis is an essential cell survival strategy to promote replication after DNA damage. The accumulation of Y family polymerases (pol) iota and Rev1 at the stalled replication machinery is mediated by the ubiquitin-binding motifs (UBMs) of the polymerases and enhanced by PCNA monoubiquitination. We report the solution structures of the C-terminal UBM of human pol iota and its comp...
متن کاملDNA-damage tolerance mediated by PCNA•Ub fusions in human cells is dependent on Rev1 but not Polη
In response to replication-blocking lesions, proliferating cell nuclear antigen (PCNA) can be sequentially ubiquitinated at the K164 residue, leading to two modes of DNA-damage tolerance, namely, translesion DNA synthesis (TLS) and error-free lesion bypass. Although the majority of reported data support a model whereby monoubiquitinated PCNA enhances its affinity for TLS polymerases and hence r...
متن کاملThe non-canonical protein binding site at the monomer-monomer interface of yeast proliferating cell nuclear antigen (PCNA) regulates the Rev1-PCNA interaction and Polζ/Rev1-dependent translesion DNA synthesis.
Rev1 and DNA polymerase ζ (Polζ) are involved in the tolerance of DNA damage by translesion synthesis (TLS). The proliferating cell nuclear antigen (PCNA), the auxiliary factor of nuclear DNA polymerases, plays an important role in regulating the access of TLS polymerases to the primer terminus. Both Rev1 and Polζ lack the conserved hydrophobic motif that is used by many proteins for the intera...
متن کاملREV1 promotes PCNA monoubiquitylation through interacting with ubiquitylated RAD18.
Translesion DNA synthesis (TLS) is a mode of DNA damage tolerance which plays an important role in genome mutagenesis and chromatin integrity maintenance. Proliferating cell nuclear antigen (PCNA) monoubiquitylation is one of the key factors for TLS pathway choice. So far, it remains unclear how the TLS pathway is elaborately regulated. Here, we report that TLS polymerase REV1 can promote PCNA ...
متن کاملVertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1
REV1 is central to the DNA damage response of eukaryotes through an as yet poorly understood role in translesion synthesis. REV1 is a member of the Y-type DNA polymerase family and is capable of in vitro deoxycytidyl transferase activity opposite a range of damaged bases. However, non-catalytic roles for REV1 have been suggested by the Saccharomyces cerevisiae rev1-1 mutant, which carries a poi...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry
سال: 2018
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2018.03.028