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DNA Damage can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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DNA Damage Can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Updated: Feb 28, 2026

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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哺乳類卵母細胞におけるDNA損傷修復に必須なレプリケーションプロテインA1†

Xiaosu Miao1, Rui Guo2,3, Andrea Williams1

  • 1Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA.

Biology of reproduction
|February 27, 2026
PubMed
まとめ

複製タンパク質A（RPA）は、発生中の卵母細胞におけるDNA修復に不可欠です。その不在は、メスマウスにおけるDNA損傷、染色体異常、および不妊を引き起こします。

キーワード:
DNA損傷染色体アライメント女性の生殖能力卵胞発生卵母細胞特異的条件付きノックアウト

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科学分野:

  • 生殖生物学
  • 分子遺伝学
  • 細胞生物学

背景:

  • 卵母細胞における未修復のDNA損傷は、遺伝的異常、流産、および不妊につながる可能性があります。
  • 複製タンパク質A（RPA）は、DNAプロセスに関与する重要な一本鎖DNA結合複合体です。

研究 の 目的:

  • 出生後の卵母細胞発生におけるDNA損傷修復におけるRPAの新規な役割を調査すること。
  • 卵母細胞におけるRPA欠損の結果を理解すること。

主な方法:

  • 生殖細胞系列特異的Creドライバー（Ddx4-CreおよびZp3-Cre）を用いた卵母細胞におけるRPA1（複製タンパク質A1）の不活性化。
  • RPA複合体の分解、DNA損傷、DNA損傷応答の活性化、染色体のアライメント、および卵胞発生を評価しました。
  • 細胞骨格の組織化に関与する遺伝子の転写レベルを分析しました。

主要な成果:

  • RPA1の枯渇は、RPA複合体の分解と、GV期卵母細胞における重度のDNA損傷につながりました。
  • RPA欠損は、DNA損傷応答経路（ATM、ATR、DNA-PK、p53）を活性化しました。
  • 染色体の不整列と卵胞発生の障害が観察され、卵母細胞数の減少と女性の不妊につながりました。

結論:

  • RPAは、哺乳類の卵母細胞形成におけるDNA損傷修復において、これまで認識されていなかった重要な役割を果たしています。
  • RPAは、卵母細胞の遺伝的完全性と女性の生殖能力の維持に不可欠です。