DNA polymerase Β is critical for mouse meiotic synapsis

Dawit Kidane, Alan S. Jonason, Timothy S. Gorton, Ivailo Mihaylov, Jing Pan, Scott Keeney, Dirk G. De Rooij, Terry Ashley, Agnes Keh, Yanfeng Liu, Urmi Banerjee, Daniel Zelterman, Joann B. Sweasy

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

We have shown earlier that DNA polymerase Β (Pol Β) localizes to the synaptonemal complex (SC) during Prophase I of meiosis in mice. Pol Β localizes to synapsed axes during zygonema and pachynema, and it associates with the ends of bivalents during late pachynema and diplonema. To test whether these localization patterns reflect a function for Pol Β in recombination and/or synapsis, we used conditional gene targeting to delete the PolB gene from germ cells. We find that Pol Β-deficient spermatocytes are defective in meiotic chromosome synapsis and undergo apoptosis during Prophase I. We also find that SPO11-dependent γH2AX persists on meiotic chromatin, indicating that Pol Β is critical for the repair of SPO11-induced double-strand breaks (DSBs). Pol Β-deficient spermatocytes yielded reduced steady-state levels of the SPO11-oligonucleotide complexes that are formed when SPO11 is removed from the ends of DSBs, and cytological experiments revealed that chromosome-associated foci of replication protein A (RPA), RAD51 and DMC1 are less abundant in Pol Β-deficient spermatocyte nuclei. Localization of Pol Β to meiotic chromosomes requires the formation of SPO11-dependent DSBs. Taken together, these findings strongly indicate that Pol Β is required at a very early step in the processing of meiotic DSBs, at or before the removal of SPO11 from DSB ends and the generation of the 3′ single-stranded tails necessary for subsequent strand exchange. The chromosome synapsis defects and Prophase I apoptosis of Pol Β-deficient spermatocytes are likely a direct consequence of these recombination defects.

Original languageEnglish (US)
Pages (from-to)410-423
Number of pages14
JournalEMBO Journal
Volume29
Issue number2
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • DNA polymerase
  • DNA repair
  • Meiosis
  • Synaptonemal complex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'DNA polymerase Β is critical for mouse meiotic synapsis'. Together they form a unique fingerprint.

Cite this