TY  - JOUR
A1  - Leal, Andrea Zurita
A1  - Schwebs, Marie
A1  - Briggs, Emma
A1  - Weisert, Nadine
A1  - Reis, Helena
A1  - Lemgruber, Leondro
A1  - Luko, Katarina
A1  - Wilkes, Jonathan
A1  - Butter, Falk
A1  - McCulloch, Richard
A1  - Janzen, Christian J.
T1  - Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation
JF  - Nucleic Acids Research
N2  - Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.
KW  - cross-link repair
KW  - cell cycle
KW  - gene expression
KW  - low fidelity
KW  - replication
KW  - bypass
KW  - theta
KW  - reveals
KW  - binding
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230579
VL  - 48
IS  - 17
ER  - 
TY  - JOUR
A1  - Rickman, Kimberly A.
A1  - Lach, Francis P.
A1  - Abhyankar, Avinash
A1  - Donovan, Frank X.
A1  - Sanborn, Erica M.
A1  - Kennedy, Jennifer A.
A1  - Sougnez, Carrie
A1  - Gabriel, Stacey B.
A1  - Elemento, Olivier
A1  - Chandrasekharappa, Settara C.
A1  - Schindler, Detlev
A1  - Auerbach, Arleen D.
A1  - Smogorzewska, Agata
T1  - Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia
JF  - Cell Reports
N2  - Fanconi anemia (FA) is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs). Mutations in 17 genes (FANCA-FANCS) have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2), UBE2T. UBE2T is known to interact with FANCL, the E3 ubiquitin-ligase component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following treatment with mitomycin C, and are hypersensitive to crosslinking agents. These cellular defects are complemented by expression of wild-type UBE2T, demonstrating that deficiency of the protein UBE2T can lead to Fanconi anemia. UBE2T gene gains an alias of FANCT.
KW  - cross-link repair
KW  - DNA repair
KW  - gene
KW  - mutations
KW  - aldehydes
KW  - somatic mosaicism
KW  - pathway
KW  - monoubiquitination
KW  - diagnosis
KW  - proteins
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151525
VL  - 12
SP  - 35
EP  - 41
ER  -