Protein Information

ID 176
Name PCNA
Synonyms Cyclin; DNA polymerase delta auxillary protein; PCNA; Proliferating cell nuclear antigen; DNA polymerase delta auxillary proteins; Proliferating cell nuclear antigens

Compound Information

ID 117
Name DDT
CAS 1,1′-(2,2,2-trichloroethylidene)bis[4-chlorobenzene]

Reference

PubMed Abstract RScore(About this table)
18284681 Brun J, Chiu R, Lockhart K, Xiao W, Wouters BG, Gray DA: hMMS2 serves a redundant role in human PCNA polyubiquitination. BMC Mol Biol. 2008 Feb 19;9:24.
BACKGROUND: In yeast, DNA damage leads to the mono and polyubiquitination of the sliding clamp PCNA. Monoubiquitination of PCNA is controlled by RAD18 (E3 ligase) and RAD6 (E2 conjugating enzyme), while the extension of the monoubiquitinated PCNA into a polyubiquitinated substrate is governed by RAD5, and the heterodimer of UBC13/MMS2. Each modification directs a different branch of the DNA damage tolerance pathway (DDT). While PCNA monoubiquitination leads to error-prone bypass via TLS, biochemical studies have identified MMS2 along with its heteromeric partner UBC13 to govern the error-free repair of DNA lesions by catalyzing the formation of lysine 63-linked polyubiquitin chains (K63-polyUb). Recently, it was shown that PCNA polyubiquitination is conserved in human cells and that this modification is dependent on RAD18, UBC13 and SHPRH. However, the role of hMMS2 in this process was not specifically addressed. RESULTS: In this report we show that mammalian cells in which MMS2 was reduced by siRNA-mediated knockdown maintains PCNA polyubiquitination while a knockdown of RAD18 or UBC13 abrogates PCNA ubiquitination. Moreover, the additional knockdown of a UEV1A (MMS2 homolog) does not deplete PCNA polyubiquitination. Finally, mouse embryonic stem cells null for MMS2 with or without the additional depletion of mUEV1A continue to polyubiquitinated PCNA with normal kinetics. CONCLUSION: Our results point to a high level of redundancy in the DDT pathway and suggest the existence of another hMMS2 variant (hMMSv) or complex that can compensate for its loss.
7(0,0,0,7)