Novel insights into RAD51 activity and regulation during homologous recombination and DNA replication

Abstract

In this review we focus on new insights that challenge our understanding of homologous recombination (HR) and Rad51 regulation. Recent advances using high resolution microscopy and single molecule techniques have broadened our knowledge of Rad51 filament formation and strand invasion at double-strand break (DSB) sites and at replication forks, which are one of most physiologically relevant forms of HR from yeast to humans. Rad51 filament formation and strand invasion is regulated by many mediator proteins such as the Rad51 paralogues and the Shu complex, consisting of a Shu2/SWS1 family member and additional Rad51 paralogues. Importantly, a novel RAD-51 paralogue was discovered in C. elegans and its in vitro characterization has demonstrated a new function for the worm RAD-51 paralogues during HR. Conservation of the human RAD51 paralogues function during HR and repair of replicative damage demonstrate how the RAD51 mediators play a critical role in human health and genomic integrity. Together, these new findings provide a framework for understanding RAD51 and its mediators in DNA repair during multiple cellular contexts.

CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair

“…S2F), while total ATM expression remained unchanged. In addition, Rad51, a single-stranded DNA-binding protein responsible for HR repair (21,22), showed modest increases in CTCF depleted cells. In contrast, the ATR kinase was only minimally affected by the knockdown (Fig.…”

Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer Resolution

“…How these modifications affect the dynamics of nucleoprotein filament assembly and stability remains to be determined. More importantly, the RAD51-DNA interactions are controlled by the recombination mediator BRCA2, by RAD51 paralogs and Shu complex (Zelensky et al, 2014, Prakash et al, 2015, Godin et al, 2016), by antirecombinogenic DNA helicases (Daley et al, 2014), and by the heteroduplex rejection machinery (Spies and Fishel, 2015). These modulators of RAD51 activity or their individual RAD51-interacting domains can be incorporated into the FRET-based, single-molecule experiments described here.…”

O-Glcnac Glycosylation of Rad51 Plays an Important Role in Promoting Colorectal Cancer Cell Invasion

“…Rad51 overexpression leads to the accumulation of abnormal karyotypes and gene mutations, which are closely related to carcinogenesis and drug resistance [16]. Studies have shown that, such as breast cancer, pancreatic cancer and other tumors overexpressed Rad51 protein, positively correlated to tumor histological grade and stage [17,18]. In addition, domestic and foreign researchers also found that gene polymorphism of Rad51 recognized as the risk factor of CRC carcinogenesis.…”