Abstract:
:Translesion DNA synthesis (TLS) by the Y-family DNA polymerases Polη, Polι and Polκ, mediated via interaction with proliferating cell nuclear antigen (PCNA), is a crucial pathway that protects human cells against DNA damage. We report that Polη has three PCNA-interacting protein (PIP) boxes (PIP1, 2, 3) that contribute differentially to two distinct functions, stimulation of DNA synthesis and promotion of PCNA ubiquitination. The latter function is strongly associated with formation of nuclear Polη foci, which co-localize with PCNA. We also show that Polκ has two functionally distinct PIP boxes, like Polη, whereas Polι has a single PIP box involved in stimulation of DNA synthesis. All three polymerases were additionally stimulated by mono-ubiquitinated PCNA in vitro. The three PIP boxes and a ubiquitin-binding zinc-finger of Polη exert redundant and additive effects in vivo via distinct molecular mechanisms. These findings provide an integrated picture of the orchestration of TLS polymerases.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Masuda Y,Kanao R,Kaji K,Ohmori H,Hanaoka F,Masutani Cdoi
10.1093/nar/gkv712subject
Has Abstractpub_date
2015-09-18 00:00:00pages
7898-910issue
16eissn
0305-1048issn
1362-4962pii
gkv712journal_volume
43pub_type
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