| Full text | |
| Author(s): |
Damasceno, Jeziel D.
[1]
;
Obonaga, Ricardo
[1]
;
Silva, Gabriel L. A.
[1]
;
Reis-Cunha, Joao L.
[2]
;
Duncan, Samuel M.
[3]
;
Bartholomeu, Daniella C.
[2]
;
Mottram, Jeremy C.
[4, 3]
;
McCulloch, Richard
[3]
;
Tosi, Luiz R. O.
[1]
Total Authors: 9
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Lab Genom Parasitos, BR-31270901 Belo Horizonte, MG - Brazil
[3] Univ Glasgow, Wellcome Ctr Mol Parasitol, Inst Infect Immun & Inflammat, Glasgow G12 8TA, Lanark - Scotland
[4] Univ York, Dept Biol, Ctr Immunol & Infect, York YO10 5DD, N Yorkshire - England
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Nucleic Acids Research; v. 46, n. 22, p. 11835-11846, DEC 14 2018. |
| Web of Science Citations: | 2 |
| Abstract | |
Leishmania species are protozoan parasites whose remarkably plastic genome limits the establishment of effective genetic manipulation and leishmaniasis treatment. The strategies used by Leishmania to maintain its genome while allowing variability are not fully understood. Here, we used DiCre-mediated conditional gene deletion to show that HUS1, a component of the 9-1-1 (RAD9-RAD1-HUS1) complex, is essential and is required for a G2/Mcheckpoint. By analyzing genome-wide instability in HUS1 ablated cells, HUS1 is shown to have a conserved role, by which it preserves genome stability and also a divergent role, by which it promotes genome variability. These roles of HUS1 are related to distinct patterns of formation and resolution of single-stranded DNA and gamma H2A, throughout the cell cycle. Our findings suggest that Leishmania 9-1-1 subunits have evolved to co-opt canonical genomic maintenance and genomic variation functions. Hence, this study reveals a pivotal function of HUS1 in balancing genome stability and transmission in Leishmania. These findings may be relevant to understanding the evolution of genome maintenance and plasticity in other pathogens and eukaryotes. (AU) | |
| FAPESP's process: | 14/00751-9 - Identification of LmRad9, LmHus1 and LmRad1-interacting proteins and generation of a LmHus1 conditional knockout cell line |
| Grantee: | Jeziel Dener Damasceno |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 17/07092-9 - How do checkpoint proteins Rad9 and Hus1 act to maintain genome stability in the protozoan Leishmania major? |
| Grantee: | Luiz Ricardo Orsini Tosi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/06824-8 - Characterization of the proteins LmRad9 and LmRad1 in the DNA damage response of Leishmania major |
| Grantee: | Luiz Ricardo Orsini Tosi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/00570-1 - Characterization of the putative 9-1-1 complex of Leishmania major |
| Grantee: | Jeziel Dener Damasceno |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 16/16454-9 - Characterization of the ATR kinase of Leishmania major and its role in DNA replication stress signaling |
| Grantee: | Gabriel Lamak Almeida da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites? |
| Grantee: | Maria Carolina Quartim Barbosa Elias Sabbaga |
| Support Opportunities: | Research Projects - Thematic Grants |