DNA polymerase η lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells Journal Article
| Authors: | Acharya, N.; Yoon, J. H.; Hurwitz, J.; Prakasha, L.; Prakasha, S. |
| Article Title: | DNA polymerase η lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells |
| Abstract: | The Rad6-Rad18 mediated monoubiquitylation of proliferating cell nuclear antigen (PCNA) at lys 164 plays a crucial role in promoting the access of translesion synthesis (TLS) DNA polymerases (Pols) to PCNA in the replication fork stalled at a lesion site. Although a number of genetic and biochemical observations have provided strong evidence that TLS Pols bind PCNA at its interdomain connector loop (IDCL) via their PCNA-interacting protein (PIP) domain, a more recent proposal formulates that TLS Pols bind PCNA at two sites, to the IDCL via their PIP domain and to lys-164 linked ubiquitin (Ub) via their ubiquitin-binding domain. To ascertain the relative contributions of the PIP and Ub-binding zinc finger (UBZ) domains of human Polη in TLS, we have determined whether the C-terminal truncations of hPolη that contain the PIP1 domain but lack the UBZ and PIP2 domains can still function in TLS in human cells. Our observations that such C-terminally truncated proteins promote efficient TLS opposite a cis-syn TT dimer and confer a high degree of UV resistance to XPV cells provide unambiguous evidence that the binding of PCNA via its PIP domain is essential as well as sufficient for providing hPolη the ability to carry out TLS in human cells. |
| Keywords: | controlled study; unclassified drug; human cell; gene deletion; mutation; dna directed dna polymerase eta; ubiquitin; dna synthesis; protein domain; protein function; dna damage; carboxy terminal sequence; protein binding; protein interaction; dna; ubiquitination; protein multimerization; protein biosynthesis; cycline; zinc finger protein; protein interaction domains and motifs; proliferating cell nuclear antigen; human pol eta; proliferating cell nuclear antigen ubiquitylation; translesion dna synthesis; ubiquitin-binding zinc finger domain; ubiquitin binding zinc finger; dna-directed dna polymerase |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 107 |
| Issue: | 23 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2010-06-08 |
| Start Page: | 10401 |
| End Page: | 10405 |
| Language: | English |
| DOI: | 10.1073/pnas.1005492107 |
| PUBMED: | 20498091 |
| PROVIDER: | scopus |
| PMCID: | PMC2890850 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus" |
