Evidence map›Paper›PMID 21228215›Full record

ArticleBiology of reproduction2011

Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in mouse spermiogenesis.

Mirella L Meyer-Ficca, Julia D Lonchar, Motomasa Ihara, Marvin L Meistrich, Caroline A Austin, Ralph G Meyer

Open access · bronzeAbstract read
In one paragraph

Article in Biology of reproduction, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
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  13. Review
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  15. Review
  16. Article
  17. TOP2B: The First Thirty Years.International journal of molecular sciences · 2018
    Review
  18. Article
  19. Understanding sperm DNA fragmentation.Translational andrology and urology · 2017
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Mirella L Meyer-FiccaDepartment of Animal Biology and Mari Lowe Center for Comparative Oncology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Julia D Lonchar
Motomasa Ihara
Marvin L Meistrich
Caroline A Austin
Ralph G Meyer
University of Pennsylvania · USNewcastle University · GBThe University of Texas MD Anderson Cancer Center · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
ADP-Ribose Polymer Metabolism in SpermatogenesisR01HD048837 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI MEYER, RALPH G · 2005 to 2009
$1.4M
NICHD NIH HHS R01 HD048837NICHD NIH HHS R01 HD48837NIEHS NIH HHS P30 ES013508NIEHS NIH HHS P30-ES013508
6 · The paper itself

Abstract

To achieve the specialized nuclear structure in sperm necessary for fertilization, dramatic chromatin reorganization steps in developing spermatids are required where histones are largely replaced first by transition proteins and then by protamines. This entails the transient formation of DNA strand breaks to allow for, first, DNA relaxation and then chromatin compaction. However, the nature and origin of these breaks are not well understood. We previously reported that these DNA strand breaks trigger the activation of poly(ADP-ribose) (PAR) polymerases PARP1 and PARP2 and that interference with PARP activation causes poor chromatin integrity with abnormal retention of histones in mature sperm and impaired embryonic survival. Here we show that the activity of topoisomerase II beta (TOP2B), an enzyme involved in DNA strand break formation in elongating spermatids, is strongly inhibited by the activity of PARP1 and PARP2 in vitro, and this is in turn counteracted by the PAR-degrading activity of PAR glycohydrolase. Moreover, genetic and pharmacological PARP inhibition both lead to increased TOP2B activity in murine spermatids in vivo as measured by covalent binding of TOP2B to the DNA. In summary, the available data suggest a functional relationship between the DNA strand break-generating activity of TOP2B and the DNA strand break-dependent activation of PARP enzymes that in turn inhibit TOP2B. Because PARP activity also facilitates histone H1 linker removal and local chromatin decondensation, cycles of PAR formation and degradation may be necessary to coordinate TOP2B-dependent DNA relaxation with histone-to-protamine exchange necessary for spermatid chromatin remodeling.

Indexed as

Chromatin Assembly and DisassemblySpermatogenesisAnimalsAntigens, NeoplasmDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA Topoisomerases, Type IIEnzyme InhibitorsEtoposideGlycoside HydrolasesMaleMiceMice, 129 StrainMice, KnockoutOsmolar ConcentrationPhenanthrenesAntigens, NeoplasmDNA-Binding ProteinsDNA Topoisomerases, Type IIEnzyme InhibitorsEtoposideGlycoside HydrolasesN-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochlorideParp1 protein, mousePhenanthrenesPoly Adenosine Diphosphate RibosePoly-ADP-Ribose Binding Proteinspoly ADP-ribose glycohydrolasePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTop2b protein, mouse

Identifiers

PMID21228215
PMCPMC3080419
OpenAlexW2129987863

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.