scholarly journals Formation of novel PRDM9 allele by indel events as possible trigger for tarsier-anthropoid split

2016 ◽  
Author(s):  
Sacha Heerschop ◽  
Hans Zischler ◽  
Stefan Merker ◽  
Dyah Perwitasari-Farajallah ◽  
Christine Driller
Keyword(s):  
Zinc Finger ◽  
Hybrid Sterility ◽  
Allelic Diversity ◽  
Strand Break ◽  
Zinc Finger Domain ◽  
Reading Frame ◽  
Allele Variant ◽  
High Allelic Diversity ◽  
And Function ◽  
Zinc Finger Array

AbstractPRDM9 is currently the sole speciation gene found in vertebrates causing hybrid sterility probably due to incompatible alleles. Its role in defining the double strand break loci during the meiotic prophase I is crucial for proper chromosome segregation. Therefore, the rapid turnover of the loci determining zinc finger array seems to be causative for incompatibilities. We here investigated the zinc finger domain-containing exon of PRDM9 in 23 tarsiers. Tarsiers, the most basal extant haplorhine primates, exhibit two frameshifting indels at the 5’-end of the array. The first mutation event interrupts the reading frame and function while the second compensates both. The fixation of this peculiar allele variant in tarsiers led to hypothesize that de‐ and reactivation of the zinc finger domain drove the speciation in early haplorhine primates. Moreover, the high allelic diversity within Tarsius point to multiple effects of genetic drift reflecting their phylogeographic history since the Miocene.

scholarly journals APLF (C2orf13) Is a Novel Component of Poly(ADP-Ribose) Signaling in Mammalian Cells

2008 ◽  
Vol 28 (14) ◽  
pp. 4620-4628 ◽  
Author(s):  
Stuart L. Rulten ◽  
Felipe Cortes-Ledesma ◽  
Liandi Guo ◽  
Natasha J. Iles ◽  
Keith W. Caldecott
Keyword(s):  
Zinc Finger ◽  
Mammalian Cells ◽  
Strand Break ◽  
Zinc Finger Domain ◽  
Chromosomal Damage ◽  
Chromosomal Dna ◽  
Fha Domain ◽  
Break Repair ◽  
Dna Strand ◽  
Tandem Zinc Finger

ABSTRACT APLF is a novel protein of unknown function that accumulates at sites of chromosomal DNA strand breakage via forkhead-associated (FHA) domain-mediated interactions with XRCC1 and XRCC4. APLF can also accumulate at sites of chromosomal DNA strand breaks independently of the FHA domain via an unidentified mechanism that requires a highly conserved C-terminal tandem zinc finger domain. Here, we show that the zinc finger domain binds tightly to poly(ADP-ribose), a polymeric posttranslational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Protein poly(ADP-ribosyl)ation is tightly regulated and defects in either its synthesis or degradation slow global rates of chromosomal single-strand break repair. Interestingly, APLF negatively affects poly(ADP-ribosyl)ation in vitro, and this activity is dependent on its capacity to bind the polymer. In addition, transient overexpression in human A549 cells of full-length APLF or a C-terminal fragment encoding the tandem zinc finger domain greatly suppresses the appearance of poly(ADP-ribose), in a zinc finger-dependent manner. We conclude that APLF can accumulate at sites of chromosomal damage via zinc finger-mediated binding to poly(ADP-ribose) and is a novel component of poly(ADP-ribose) signaling in mammalian cells.

scholarly journals Cataloging Human PRDM9 Allelic Variation Using Long-Read Sequencing Reveals PRDM9 Population Specificity and Two Distinct Groupings of Related Alleles

2021 ◽  
Vol 9 ◽  
Author(s):  
Benjamin Alleva ◽  
Kevin Brick ◽  
Florencia Pratto ◽  
Mini Huang ◽  
Rafael Daniel Camerini-Otero
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Meiotic Recombination ◽  
Allelic Variation ◽  
Allelic Diversity ◽  
Double Strand Breaks ◽  
Human Populations ◽  
Strand Breaks ◽  
Long Read ◽  
Zinc Finger Array

The PRDM9 protein determines sites of meiotic recombination in humans by directing meiotic DNA double-strand breaks to specific loci. Targeting specificity is encoded by a long array of C2H2 zinc fingers that bind to DNA. This zinc finger array is hypervariable, and the resulting alleles each have a potentially different DNA binding preference. The assessment of PRDM9 diversity is important for understanding the complexity of human population genetics, inheritance linkage patterns, and predisposition to genetic disease. Due to the repetitive nature of the PRDM9 zinc finger array, the large-scale sequencing of human PRDM9 is challenging. We, therefore, developed a long-read sequencing strategy to infer the diploid PRDM9 zinc finger array genotype in a high-throughput manner. From an unbiased study of PRDM9 allelic diversity in 720 individuals from seven human populations, we detected 69 PRDM9 alleles. Several alleles differ in frequency among human populations, and 32 alleles had not been identified by previous studies, which were heavily biased to European populations. PRDM9 alleles are distinguished by their DNA binding site preferences and fall into two major categories related to the most common PRDM9-A and PRDM9-C alleles. We also found that it is likely that inter-conversion between allele types is rare. By mapping meiotic double-strand breaks (DSBs) in the testis, we found that small variations in PRDM9 can substantially alter the meiotic recombination landscape, demonstrating that minor PRDM9 variants may play an under-appreciated role in shaping patterns of human recombination. In summary, our data greatly expands knowledge of PRDM9 diversity in humans.

Hsp70 Escort Protein: More Than a Regulator of Mitochondrial Hsp70

2018 ◽  
Vol 16 (1) ◽  
pp. 64-73 ◽  
Author(s):  
David O. Nyakundi ◽  
Stephen J. Bentley ◽  
Aileen Boshoff
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Domain ◽  
C Terminus ◽  
Cellular Localisation ◽  
The Matrix ◽  
Mitochondrial Hsp70 ◽  
Cellular Compartments ◽  
Intramolecular Communication ◽  
Self Aggregation ◽  
J Protein

Hsp70 members occupy a central role in proteostasis and are found in different eukaryotic cellular compartments. The mitochondrial Hsp70/J-protein machinery performs multiple functions vital for the proper functioning of the mitochondria, including forming part of the import motor that transports proteins from the cytosol into the matrix and inner membrane, and subsequently folds these proteins in the mitochondria. However, unlike other Hsp70s, mitochondrial Hsp70 (mtHsp70) has the propensity to self-aggregate, accumulating as insoluble aggregates. The self-aggregation of mtHsp70 is caused by both interdomain and intramolecular communication within the ATPase and linker domains. Since mtHsp70 is unable to fold itself into an active conformation, it requires an Hsp70 escort protein (Hep) to both inhibit self-aggregation and promote the correct folding. Hep1 orthologues are present in the mitochondria of many eukaryotic cells but are absent in prokaryotes. Hep1 proteins are relatively small and contain a highly conserved zinc-finger domain with one tetracysteine motif that is essential for binding zinc ions and maintaining the function and solubility of the protein. The zinc-finger domain lies towards the C-terminus of Hep1 proteins, with very little conservation outside of this domain. Other than maintaining mtHsp70 in a functional state, Hep1 proteins play a variety of other roles in the cell and have been proposed to function as both chaperones and co-chaperones. The cellular localisation and some of the functions are often speculative and are not common to all Hep1 proteins analysed to date.

scholarly journals Unexpectedly High Allelic Diversity at the KIT Locus Causing Dominant White Color in the Domestic Pig

Genetics ◽  
2002 ◽  
Vol 160 (1) ◽  
pp. 305-311
Author(s):  
G Pielberg ◽  
C Olsson ◽  
A-C Syvänen ◽  
L Andersson
Keyword(s):  
Coat Color ◽  
Allelic Diversity ◽  
Growth Factor Receptor ◽  
Small Sample ◽  
Color Variation ◽  
Large White ◽  
High Genetic Diversity ◽  
High Allelic Diversity ◽  
Stem Cell Growth Factor ◽  
New Alleles

Abstract Mutations in KIT encoding the mast/stem cell growth factor receptor (MGF) are responsible for coat color variation in domestic pigs. The dominant white phenotype is caused by two mutations, a gene duplication and a splice mutation in one of the copies leading to skipping of exon 17. Here we applied minisequencing and pyrosequencing for quantitative analysis of the number of copies with the splice form. An unexpectedly high genetic diversity was revealed in white pigs. We found four different KIT alleles in a small sample of eight Large White females used as founder animals in a wild boar intercross. A similar number of KIT alleles was found in commercial populations of white Landrace and Large White pigs. We provide evidence for at least two new KIT alleles in pigs, both with a triplication of the gene. The results imply that KIT alleles with the duplication are genetically unstable and new alleles are most likely generated by unequal crossing over. This study provides an improved method for genotyping the complicated Dominant white/KIT locus in pigs. The results also suggest that some alleles may be associated with negative pleiotropic effects on other traits.

scholarly journals The ANGULATA 7 gene encodes a DnaJ‐like zinc finger‐domain protein involved in chloroplast function and leaf development in Arabidopsis

2017 ◽  
Vol 89 (5) ◽  
pp. 870-884 ◽  
Author(s):  
Tamara Muñoz‐Nortes ◽  
José Manuel Pérez‐Pérez ◽  
María Rosa Ponce ◽  
Héctor Candela ◽  
José Luis Micol
Keyword(s):  
Zinc Finger ◽  
Leaf Development ◽  
Zinc Finger Domain ◽  
Domain Protein

scholarly journals Crystal structure of zinc‐finger domain of Nanos and its functional implications

EMBO Reports ◽  
2010 ◽  
Vol 11 (11) ◽  
pp. 848-853 ◽  
Author(s):  
Hiroshi Hashimoto ◽  
Kodai Hara ◽  
Asami Hishiki ◽  
Shigeta Kawaguchi ◽  
Naoki Shichijo ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Zinc Finger ◽  
Zinc Finger Domain ◽  
Functional Implications

Characterization of the DNA Binding Activity of the ZFY Zinc Finger Domain

Biochemistry ◽  
2010 ◽  
Vol 49 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jennifer Grants ◽  
Erin Flanagan ◽  
Andrea Yee ◽  
Paul J. Romaniuk
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Binding Activity ◽  
Zinc Finger Domain ◽  
Dna Binding Activity
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