Regulation of translesion DNA synthesis: Posttranslational modification of lysine residues in key proteins

Abstract

Posttranslational modification of proteins often controls various aspects of their cellular function. Indeed, over the past decade or so, it has been discovered that posttranslational modification of lysine residues plays a major role in regulating translesion DNA synthesis (TLS) and perhaps the most appreciated lysine modification is that of ubiquitination. Much of the recent interest in ubiquitination stems from the fact that proliferating cell nuclear antigen (PCNA) was previously shown to be specifically ubiquitinated at K164 and that such ubiquitination plays a key role in regulating TLS. In addition, TLS polymerases themselves are now known to be ubiquitinated. In the case of human polymerase η, ubiquitination at four lysine residues in its C-terminus appears to regulate its ability to interact with PCNA and modulate TLS. Within the past few years, advances in global proteomic research has revealed that many proteins involved in TLS are, in fact, subject to a previously underappreciated number of lysine modifications. In this review, we will summarize the known lysine modifications of several key proteins involved in TLS; PCNA and Y-family polymerases η, ι, κ and Rev1 and we will discuss the potential regulatory effects of such modification in controlling TLS in vivo.

Eukaryotic DNA Polymerases in Homologous Recombination

“…During TLS, monoubiquitylation of PCNA assists in the recruitment of S. cerevisiae Pol η and Rev1 to lesions (87). However, monoubiquitylation of PCNA is not required for the function of Rev1/Pol ζ in HR (133).…”

Translesion DNA polymerases in eukaryotes: what makes them tick?

“…In the past two decades, we have witnessed a rapid expansion of TLS research and multiple comprehensive review papers focusing on the various aspects of the TLS mechanism and biological functions of the TLS polymerases have been published [relevant reviews published during the past five last years include: (Boiteux and Jinks-Robertson, 2013; Fuchs and Fujii, 2013; Goodman and Woodgate, 2013; Guengerich et al , 2015; Hedglin and Benkovic, 2015; Ishino and Ishino, 2014; Jansen et al , 2015; Lambert and Lambert, 2015; Malkova and Haber, 2012; Maxwell and Suo, 2014; McIntyre and Woodgate, 2015; Nicolay et al , 2012b; Sale, 2013; Salehan and Morse, 2013; Sharma and Canman, 2012; Sharma et al , 2013; Tomasso et al , 2014; Yang et al , 2013; Yang, 2014)]. In the current review, we intend to present the major recent findings by putting them in an historical context and by focusing on the development of the ideas leading to the current understanding of TLS.…”

Biophysical characterization of the interaction between FAAP20‐UBZ4 domain and Rev1‐BRCT domain

“…A recent study reported that monoubiquitination of Rev1 enhances the interaction between FAAP20 and Rev1, suggesting that the ubiquitin binding motif (UBM) of Rev1 (residues 933-1041) either promotes monoubiquitination of Rev1 per se or stabilizes the conjugated ubiquitin [9]. Interestingly, a recent review mentioned that the Rev1 ubiquitination sites are located near, or within, the BRCT [16]. In addition, Kim et al also showed that both FAAP20 wild type and the UBZ mutant coimmunoprecipitated with Rev1 [9], suggesting that the interaction between FAAP20 and Rev1 can be mediated through the other interfaces as well as the interaction of UBZ4 bound to ubiquitin with BRCT.…”