showing 4 related works from this author
RNase H1 and H2 are differentially regulated to eliminate RNA-DNA hybrids
2019
SUMMARYRNA-DNA hybrids are tightly regulated to ensure genome integrity. The RNase H enzymes, RNase H1 and H2, contribute to chromosomal stability through the removal of RNA-DNA hybrids. Loss of RNase H2 function is implicated in human diseases of the nervous system and cancer. To better understand RNA-DNA hybrid dynamics, we have focused on elucidating the regulation of the RNase H enzymes themselves. Using yeast as a model system, we demonstrate that RNase H1 and H2 are controlled in different manners. RNase H2 is regulated in a strict cell cycle dependent manner, both in terms of its R-loop removal, and ribonucleotide excision repair functions. RNase H1, however, can function independent…
RNase H1 and H2 Are Differentially Regulated to Process RNA-DNA Hybrids
2019
Summary: RNA-DNA hybrids are tightly regulated to ensure genome integrity. The RNase H enzymes RNase H1 and H2 contribute to chromosomal stability through the removal of RNA-DNA hybrids. Loss of RNase H2 function is implicated in human diseases of the nervous system and cancer. To better understand RNA-DNA hybrid dynamics, we focused on elucidating the regulation of the RNase H enzymes themselves. Using yeast as a model system, we demonstrate that RNase H1 and H2 are controlled in different manners. RNase H2 has strict cell cycle requirements, in that it has an essential function in G2/M for both R-loop processing and ribonucleotide excision repair. RNase H1, however, can function independe…
African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system
2019
Significance Many parasites escape the host immune system by undergoing antigenic variation, a process in which surface antigens are regularly shed and replaced by new ones. Trypanosoma brucei employs multiple sophisticated molecular mechanisms to ensure the expression of a homogeneous VSG coat. We generated a mutant parasite that expresses multiple distinct VSGs and studied the consequences of having a multi-VSG coat during an infection. We showed that expression of multiple VSGs makes the parasites more vulnerable to the immune response, which can now control the trypanosomes from the onset of the infection, allowing most mice to survive. In the future, trypanosome infections may be treat…
A long non-coding RNA controls parasite differentiation in African trypanosomes
2020
Trypanosoma bruceicauses African sleeping sickness, a fatal human disease. Its differentiation from replicative slender form into quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation. To determine whether lncRNAs are involved in parasite differentiation we used RNAseq to survey theT. bruceilncRNA gene repertoire, identifying 1,428 previously uncharacterized lncRNA genes. We analysedgrumpy, a lncRNA located immediately upstream of an RNA-binding protein that is akeydifferentiation regulator. Grumpy over-expression resulted in premature parasite differentiation into the quiescent stumpy form, and subse…