BRCA1 preserves genome integrity during the formation of undifferentiated spermatogonia.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-08-01 Epub Date: 2025-05-28 DOI:10.1038/s44319-025-00487-5

Peng Li, Licun Song, Longfei Ma, Chunsheng Han, Lejun Li, Lin-Yu Lu, Yidan Liu

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Abstract

Undifferentiated spermatogonia, which form shortly after birth, consist of spermatogonial stem cells and progenitor spermatogonia that maintain homeostasis. As the origin of spermatogenesis, undifferentiated spermatogonia must preserve genome integrity. Paradoxically, we demonstrate that massive spontaneous DNA damage, potentially generated by formaldehyde, arises during the formation of undifferentiated spermatogonia, posing a significant threat to genome integrity. We further reveal that BRCA1 is essential for the timely repair of this spontaneous DNA damage. BRCA1 loss leads to a dramatic reduction in progenitor spermatogonia and disrupts the formation of undifferentiated spermatogonia. Although spermatogonial stem cells initially undergo hyperproliferation, they are eventually depleted, resulting in the premature exhaustion of undifferentiated spermatogonia. Our study highlights a striking difference in DNA damage sensitivity between the two populations of undifferentiated spermatogonia and underscores the critical role of BRCA1-dependent DNA damage repair in preserving genome integrity during the formation of undifferentiated spermatogonia.

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BRCA1在未分化精原细胞形成过程中保持了基因组的完整性。

未分化精原细胞是在出生后不久形成的，由维持体内平衡的精原干细胞和祖精原细胞组成。未分化精原体作为精子发生的起源，必须保持基因组的完整性。矛盾的是，我们证明了大量的自发DNA损伤，可能是由甲醛产生的，在未分化精原细胞的形成过程中出现，对基因组完整性构成重大威胁。我们进一步发现BRCA1对于及时修复这种自发DNA损伤至关重要。BRCA1缺失导致祖精原细胞显著减少，破坏未分化精原细胞的形成。尽管精原干细胞最初经历过度增殖，但它们最终被耗尽，导致未分化的精原细胞过早衰竭。我们的研究强调了两个未分化精原细胞群体之间DNA损伤敏感性的显著差异，并强调了brca1依赖性DNA损伤修复在未分化精原细胞形成过程中保持基因组完整性的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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