The RAD51 recombinase protects mitotic chromatin in human cells

Wassing, Isabel E.; Graham, Emily B.; Saayman, Xanita; Rampazzo, Lucia; Ralf, Christine; Bassett, Andrew; Esashi, Fumiko

doi:10.1038/s41467-021-25643-y

Cited by 31 publications

(26 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RAD51 also plays non-repair functions, which stimulates replication forks reversal and stabilizes stalled forks [ 35 ]. RAD51 promotes mitotic DNA synthesis and successful chromosome segregation in mitosis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

RAD51 is essential for spermatogenesis and male fertility in mice

et al. 2022

View full text Add to dashboard Cite

The recombinase RAD51 catalyzes the DNA strand exchange reaction in homologous recombination (HR) during both mitosis and meiosis. However, the physiological role of RAD51 during spermatogenesis remains unclear since RAD51 null mutation is embryonic lethal in mice. In this study, we generated a conditional knockout mouse model to study the role of RAD51 in spermatogenesis. Conditional disruption of RAD51 in germ cells by Vasa-Cre led to spermatogonial loss and Sertoli cell-only syndrome. Furthermore, tamoxifen-inducible RAD51 knockout by UBC-CreERT2 confirmed that RAD51 deletion led to early spermatogenic cells loss and apoptosis. Notably, inducible knockout of RAD51 in adult mice caused defects in meiosis, with accumulated meiotic double-strand breaks (DSBs), reduced numbers of pachytene spermatocytes and less crossover formation. Our study revealed an essential role for Rad51 in the maintenance of spermatogonia as well as meiotic progression in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

RAD51 is essential for spermatogenesis and male fertility in mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This process is enhanced in human cells expressing Rad51-K133 and is regulated by Polo-like kinase 1, which induces Rad51 recruitment to ssDNA upon phosphorylation. These results suggest a non-recombinogenic role for Rad51 in MiDAS by protecting stalled forks against nucleases [91].…”

Section: Non-recombinogenic Roles Of Rad51 Brca2 and Rad52 In The Dynamics Of Reversed Forksmentioning

confidence: 74%

Non-Recombinogenic Functions of Rad51, BRCA2, and Rad52 in DNA Damage Tolerance

Prado

2021

Genes

View full text Add to dashboard Cite

The DNA damage tolerance (DDT) response is aimed to timely and safely complete DNA replication by facilitating the advance of replication forks through blocking lesions. This process is associated with an accumulation of single-strand DNA (ssDNA), both at the fork and behind the fork. Lesion bypass and ssDNA filling can be performed by translation synthesis (TLS) and template switching mechanisms. TLS uses low-fidelity polymerases to incorporate a dNTP opposite the blocking lesion, whereas template switching uses a Rad51/ssDNA nucleofilament and the sister chromatid to bypass the lesion. Rad51 is loaded at this nucleofilament by two mediator proteins, BRCA2 and Rad52, and these three factors are critical for homologous recombination (HR). Here, we review recent advances showing that Rad51, BRCA2, and Rad52 perform some of these functions through mechanisms that do not require the strand exchange activity of Rad51: the formation and protection of reversed fork structures aimed to bypass blocking lesions, and the promotion of TLS. These findings point to the central HR proteins as potential molecular switches in the choice of the mechanism of DDT.

show abstract

“…It also implies that reduced mitotic DNA synthesis may result from gross changes in replication dynamics. Recently, another key recombination factor, RAD51, was reported to promote MiDAS ( Wassing et al., 2021 ). Like RAD52, RAD51 functions in fork protection/recovery during interphase.…”

Section: Resultsmentioning

confidence: 99%