HLTF and SHPRH are not essential for PCNA polyubiquitination, survival and somatic hypermutation: Existence of an alternative E3 ligase

DNA damage tolerance is regulated at least in part at the level of proliferating cell nuclear antigen (PCNA) ubiquitination. Monoubiquitination (PCNA-Ub) at lysine residue 164 (K164) stimulates error-prone translesion synthesis (TLS), Rad5-dependent polyubiquitination (PCNA-Ub n) stimulates error-fr...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	DNA repair Ročník 10; číslo 4; s. 438 - 444
Hlavní autoři:	Krijger, Peter H.L., Lee, Kyoo-Young, Wit, Niek, van den Berk, Paul C.M., Wu, Xiaoli, Roest, Henk P., Maas, Alex, Ding, Hao, Hoeijmakers, Jan H.J., Myung, Kyungjae, Jacobs, Heinz
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Amsterdam Elsevier B.V 03.04.2011 Elsevier
Témata:	Animals B-Lymphocytes - drug effects B-Lymphocytes - metabolism Bacteriology Biological and medical sciences Cell Survival - drug effects Cell Survival - genetics Cell Survival - radiation effects Cross-Linking Reagents - pharmacology DNA Helicases - deficiency DNA Helicases - genetics DNA Helicases - metabolism Embryonic Stem Cells - metabolism Fundamental and applied biological sciences. Psychology Gene Knockdown Techniques Gene Order Gene Targeting Growth, nutrition, cell differenciation HLTF Immunoglobulin Class Switching - drug effects Lipopolysaccharides - pharmacology Mice Mice, Knockout Microbiology Molecular and cellular biology Molecular genetics Mutagenesis. Repair PCNA Proliferating Cell Nuclear Antigen - genetics Proliferating Cell Nuclear Antigen - metabolism RAD5 SHPRH Somatic hypermutation Somatic Hypermutation, Immunoglobulin - genetics Transcription Factors - deficiency Transcription Factors - genetics Transcription Factors - metabolism Translesion synthesis Ubiquitin-Protein Ligases - metabolism Ubiquitination - genetics Ubiquitination - physiology Ubiquitination - radiation effects Ultraviolet Rays - adverse effects SHPRH Somatic hypermutation PCNA Translesion synthesis RAD5 HLTF Immunoglobulins Carbon-nitrogen ligases Enzyme Survival Ligases DNA Repair Ubiquitin-protein ligase
ISSN:	1568-7864, 1568-7856, 1568-7856
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	DNA damage tolerance is regulated at least in part at the level of proliferating cell nuclear antigen (PCNA) ubiquitination. Monoubiquitination (PCNA-Ub) at lysine residue 164 (K164) stimulates error-prone translesion synthesis (TLS), Rad5-dependent polyubiquitination (PCNA-Ub n) stimulates error-free template switching (TS). To generate high affinity antibodies by somatic hypermutation (SHM), B cells profit from error-prone TLS polymerases. Consistent with the role of PCNA-Ub in stimulating TLS, hypermutated B cells of PCNA K164R mutant mice display a defect in generating selective point mutations. Two Rad5 orthologs, HLTF and SHPRH have been identified as alternative E3 ligases generating PCNA-Ub n in mammals. As PCNA-Ub and PCNA-Ub n both make use of K164, error-free PCNA-Ub n-dependent TS may suppress error-prone PCNA-Ub-dependent TLS. To determine a regulatory role of Shprh and Hltf in SHM, we generated Shprh/ Hltf double mutant mice. Interestingly, while the formation of PCNA-Ub and PCNA-Ub n is prohibited in PCNA K164R MEFs, the formation of PCNA-Ub n is not abolished in Shprh/Hltf mutant MEFs. In line with these observations Shprh/Hltf double mutant B cells were not hypersensitive to DNA damage. Furthermore, SHM was normal in Shprh/Hltf mutant B cells. These data suggest the existence of an alternative E3 ligase in the generation of PCNA-Ub n.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 These authors contributed equally.
ISSN:	1568-7864 1568-7856 1568-7856
DOI:	10.1016/j.dnarep.2010.12.008