The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA,FEBS Letters

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The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA
FEBS Letters ( IF 3.0 ) Pub Date : 2022-05-19 , DOI: 10.1002/1873-3468.14406
Bhawna Singh _{1,

2} , Shalini Roy Chowdhury ₁ , Mohammad Shoab Mansuri ₁ , Saraswathi Jayarajan Pillai ₁ , Sonam Mehrotra _{1,

2}

Affiliation

DNA replication stress is characterized by impaired replication fork progression, causing some of the replication forks to collapse and form DNA breaks. It is a primary cause of genomic instability leading to oncogenic transformation. The repair-independent functions of the proteins RAD51 and BRCA2, which are involved in homologous recombination (HR)-mediated DNA repair, are crucial for protecting nascent DNA strands from nuclease-mediated degradation. The BRCA2 and CDKN1A-interacting protein (BCCIP) associates with BRCA2 and RAD51 during HR-mediated DNA repair. Here, we investigated the role of BCCIP during the replication stress response. We find that in the presence of replication stress, BCCIP deficiency increases replication fork stalling and results in DNA double-strand break formation. We show that BCCIP is recruited to stalled replication forks and prevents MRE11 nuclease-mediated degradation of nascent DNA strands.

中文翻译：

BRCA2 和 CDKN1A 相互作用蛋白 (BCCIP) 可稳定停滞的复制叉并防止新生 DNA 的降解

DNA 复制压力的特点是复制叉进程受损，导致一些复制叉塌陷并形成 DNA 断裂。它是导致致癌转化的基因组不稳定的主要原因。参与同源重组 (HR) 介导的 DNA 修复的蛋白质 RAD51 和 BRCA2 的修复独立功能对于保护新生 DNA 链免受核酸酶介导的降解至关重要。在 HR 介导的 DNA 修复过程中，BRCA2 和 CDKN1A 相互作用蛋白 (BCCIP) 与 BRCA2 和 RAD51 相关联。在这里，我们研究了 BCCIP 在复制应激反应中的作用。我们发现，在存在复制压力的情况下，BCCIP 缺乏会增加复制叉停滞并导致 DNA 双链断裂形成。

更新日期：2022-05-19

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