Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability

RPA 和 RAD51 维持基因组稳定性的分子调节剂

基本信息

  • 批准号:
    10541201
  • 负责人:
  • 金额:
    $ 32.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-01 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

DNA damage constitutes a major threat to genetic integrity, and has thus been implicated in the pathogenesis of cancer. Elucidating the mechanism safeguarding genome stability is important for understanding the mechanism underlying carcinogenesis. Genome integrity is constantly threatened by endogenous and exogenous agents arising from cellular metabolic processes as well as environmental exposure, many of which impede normal DNA replication and cause replication fork stalling. Stalled forks need to be properly repaired and rescued to prevent DNA lesions and genome instabilities that contribute to tumorigenesis. To repair and rescue stalled replication, a network of proteins regulating DNA damage response, DNA repair, replication, and cell cycle checkpoints are activated in response to stalled replication in order to stabilize and restart stalled forks. However, the mechanism underlying fork repair is poorly understood. Recent studies have revealed that the balance and dynamics of RAD51 and RPA at stalled forks are crucial for fork stabilization and restart. Yet how RAD51 and RPA activities are modulated remains largely elusive. Our recent findings suggest that the high-affinity single-stranded DNA binding protein complex known as CST may be a new modulator for RPA and RAD51 at GC-rich repetitive sequences in response to replication stress. The objective of this proposal is to understand the molecular relationship between CST, RAD51 and RPA in fork rescue, with the goal to provide novel insights into how cells counteract DNA damage caused by genotoxins. We propose to integrate advanced biochemical, cell biological, cell imaging, and next-gen sequencing techniques to examine how CST may regulate RPA binding at stalled sites and maintain fork progression and stability under stress (Aim 1), define how CST may modulate RAD51 activity at GC-rich stalled sites (Aim 2), and characterize the regulatory role of a surface-exposed region of CST in regulating RAD51 and RPA activities (Aim 3). Findings from the proposed research will provide novel information on the mechanism of genome stability maintenance of rescuing stalled replication and preserving genome stability.
DNA损伤是对遗传完整性的重大威胁,因此已被牵连到

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Intrinsically Disordered Region in the Human STN1 OB-Fold Domain Is Important for Protecting Genome Stability.
  • DOI:
    10.3390/biology10100977
  • 发表时间:
    2021-09-28
  • 期刊:
  • 影响因子:
    4.2
  • 作者:
    Chai W;Chastain M;Shiva O;Wang Y
  • 通讯作者:
    Wang Y
Crosstalk between CST and RPA regulates RAD51 activity during replication stress.
  • DOI:
    10.1038/s41467-021-26624-x
  • 发表时间:
    2021-11-05
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Lei KH;Yang HL;Chang HY;Yeh HY;Nguyen DD;Lee TY;Lyu X;Chastain M;Chai W;Li HW;Chi P
  • 通讯作者:
    Chi P
CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.
  • DOI:
    10.1038/s41467-023-43685-2
  • 发表时间:
    2023-11-30
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Jaiswal, Rishi Kumar;Lei, Kai-Hang;Chastain, Megan;Wang, Yuan;Shiva, Olga;Li, Shan;You, Zhongsheng;Chi, Peter;Chai, Weihang
  • 通讯作者:
    Chai, Weihang
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Weihang Chai其他文献

Weihang Chai的其他文献

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{{ truncateString('Weihang Chai', 18)}}的其他基金

Molecular Basis of Coats Plus Disease
Coats Plus 疾病的分子基础
  • 批准号:
    10607126
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
Molecular Basis of Coats Plus Disease
Coats Plus 疾病的分子基础
  • 批准号:
    10797782
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
Identification of a novel tumor suppressorof melanoma and UV-induced genome instability
黑色素瘤的新型肿瘤抑制因子和紫外线诱导的基因组不稳定性的鉴定
  • 批准号:
    10539561
  • 财政年份:
    2022
  • 资助金额:
    $ 32.92万
  • 项目类别:
Role of Telomerase is DSB Repair
端粒酶的作用是 DSB 修复
  • 批准号:
    10052953
  • 财政年份:
    2019
  • 资助金额:
    $ 32.92万
  • 项目类别:
Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability
RPA 和 RAD51 维持基因组稳定性的分子调节剂
  • 批准号:
    10153729
  • 财政年份:
    2019
  • 资助金额:
    $ 32.92万
  • 项目类别:
Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability
RPA 和 RAD51 维持基因组稳定性的分子调节剂
  • 批准号:
    10055860
  • 财政年份:
    2019
  • 资助金额:
    $ 32.92万
  • 项目类别:
Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability
RPA 和 RAD51 维持基因组稳定性的分子调节剂
  • 批准号:
    10322742
  • 财政年份:
    2019
  • 资助金额:
    $ 32.92万
  • 项目类别:
Role of human CST in preventing telomere loss
人类 CST 在预防端粒丢失中的作用
  • 批准号:
    9145437
  • 财政年份:
    2015
  • 资助金额:
    $ 32.92万
  • 项目类别:
Mechanisms of fork restart in response to genotoxic stress
响应基因毒性应激的分叉重启机制
  • 批准号:
    8800247
  • 财政年份:
    2014
  • 资助金额:
    $ 32.92万
  • 项目类别:
Mechanisms of fork restart in response to genotoxic stress
响应基因毒性应激的分叉重启机制
  • 批准号:
    9551636
  • 财政年份:
    2014
  • 资助金额:
    $ 32.92万
  • 项目类别:

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