Phase separation in DNA double-strand break response

ABSTRACT

DNA double-strand break (DSB) is the most dangerous type of DNA damage, which may lead to cell death or oncogenic mutations. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are two typical DSB repair mechanisms. Recently, many studies have revealed that liquid–liquid phase separation (LLPS) plays a pivotal role in DSB repair and response. Through LLPS, the crucial biomolecules are quickly recruited to damaged sites with a high concentration to ensure DNA repair is conducted quickly and efficiently, which facilitates DSB repair factors activating downstream proteins or transmitting signals. In addition, the dysregulation of the DSB repair factor’s phase separation has been reported to promote the development of a variety of diseases. This review not only provides a comprehensive overview of the emerging roles of LLPS in the repair of DSB but also sheds light on the regulatory patterns of phase separation in relation to the DNA damage response (DDR).

KEYWORDS:

• DNA damage response (DDR)
• DNA double-strand break (DSB)
• liquid-liquid phase separation (LLPS)
• condensates
• homologous recombination (HR)
• nonhomologous end-joining (NHEJ)

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Author contributions

X.J.F. and X.B.W. conceived this review, H.L.L., H.N., W.W.Z., X.J.F. and X.B.W. wrote the manuscript. All authors read and approved the final manuscript.

Data availability statement

The data that support the findings of this study are openly available in figshare at http://doi.org/10.6084/m9.figshare.23671068.

Additional information

Funding

The work was supported by the the National Science Fund for Distinguished Young Scholars [82225040]; Guangdong Natural Science Funds for Distinguished Young Scholars [2021B1515020022]; the National Science Fund for Excellent Young Scholars [82122057]; the National Natural Science Foundation of China [32000135].