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Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

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dc.contributor.authorGopalakrishnan, Anusha M.
dc.contributor.authorAly, Ahmed Sayed Ibrahım
dc.contributor.authorAravind, L.
dc.contributor.authorKumar, Nirbhay
dc.contributor.institutionauthorALY, AHMED SAYED IBRAHıM
dc.date.accessioned2020-10-29T23:04:53Z
dc.date.available2020-10-29T23:04:53Z
dc.date.issued2017-07-01T00:00:00Z
dc.description.abstractIn sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C2H2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (P 95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patterns (H3K9, H3K14, and H4K16). Reduced DNA damage and reduced expression of topoisomerase-like Spo11 in the KO parasites with normal Rad51 expression further suggest a functional role for PbZfp during genetic recombination that involves DNA double-strand break (DSB) formation followed by DNA repair. These finding raise the possibility of some convergent similarities of PbZfp functions to functions of mammalian PRDM9, also a C2H2 ZnF protein with histone 3 lysine 4 (H3K4) methyltransferase activity. These functions include the major role played by the latter in binding recombination hotspots in the genome during meiosis and trimethylation of the associated histones and subsequent chromatin recruitment of topoisomerase-like Spo11 to catalyze DNA DSB formation and DMC1/Rad51-mediated DNA repair and homologous recombination.
dc.identifier.citationGopalakrishnan A. M. , Aly A. S. I. , Aravind L., Kumar N., -Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response-, MBIO, cilt.8, 2017
dc.identifier.doi10.1128/mbio.01298-17
dc.identifier.scopus85029185643
dc.identifier.urihttp://hdl.handle.net/20.500.12645/26885
dc.identifier.wosWOS:000409384300030
dc.titleMultifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response
dc.typeArticle
dspace.entity.typePublication
local.avesis.idcea56fe0-e0df-49fd-bc88-c86ef7ca2243
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
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relation.isAuthorOfPublication.latestForDiscovery47a38002-6a0b-4c36-b83d-773a943d999d
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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