Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in VSports app下载. gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Review
. 2014 Jan;181(1):1-8.
doi: 10.1667/RR13572.1. Epub 2013 Dec 9.

Role of 53BP1 in the regulation of DNA double-strand break repair pathway choice

Arun Gupta  1 , Clayton R Hunt, Sharmistha Chakraborty, Raj K Pandita, John Yordy, Deepti B Ramnarain, Nobuo Horikoshi, Tej K Pandita
Affiliations
Review

Role of 53BP1 in the regulation of DNA double-strand break repair pathway choice (VSports最新版本)

Arun Gupta et al. Radiat Res. 2014 Jan.

Abstract

The p53-binding protein 1 (53BP1) is a well-known DNA damage response (DDR) factor, which is recruited to nuclear structures at the site of DNA damage and forms readily visualized ionizing radiation (IR) induced foci. Depletion of 53BP1 results in cell cycle arrest in G2/M phase as well as genomic instability in human as well as mouse cells. Within the DNA damage response mechanism, 53BP1 is classified as an adaptor/mediator, required for processing of the DNA damage response signal and as a platform for recruitment of other repair factors. More recently, specific 53BP1 contributions to DSB repair pathway choice have been recognized and are being characterized VSports手机版. In this review, we have summarized recent advances in understanding the role of 53BP1 in regulating DNA DSBs repair pathway choice, variable diversity joining [V(D)J] recombination and class-switch recombination (CSR). .

PubMed Disclaimer

"VSports app下载" Figures

FIG. 1
FIG. 1
Domain structure of 53BP1. The protein has 1972 amino acids within which four major domains have been identified: OLIG, GAR, UDR and BRCT. The UDR domain ranges from amino acids 1480 to 1616 and has two subdomains tudor and RCTD. The BRCT domain ranges from amino acid 1714 to 1972 and interacts with specific phospho-proteins (p-Proteins). There are 28 SQ/TQ phosphorylation sites within the N-terminal region and PTIP interacts with pS25 while RIF1 interacts with multiple phosphorylated SQ/TQ amino acids.
FIG. 2
FIG. 2
Role of 53BP1 during the cell cycle. 53BP1 mediates the recruitment of factors in the cell cycle G1 phase that play a role in NHEJ, V(D)J and CSR. During S phase after exposure to DNA damaging agents, ATM/MOF-dependent phosphorylated 53BP1 interacts with RIF1, which is critical for intra-S-phase checkpoint activation. Release of 53BP1 from DNA DSB sites allows BRCA1 during S/G2 phase recruitment of the HR-related proteins required for DNA end resection.
FIG. 3
FIG. 3
53BP1 interacts with chromatin to enhance NHEJ and suppress HR. Chromatin associated proteins like ATM, MOF and TIP60 facilitate the recruitment of proteins involved in DNA DSB repair through modifications of 53BP1, which is bound to chromatin through direct interaction with H4K20me2 sites. ATM dependent phosphorylation of N-terminal 53BP1 sites is required for RIF1 (28 pSQ/TQ) and PTIP (pSer-25) recruitment to DNA DSB sites. RIF1 accumulation at DSB sites antagonizes BRCA1-CtIP complex recruitment, thus suppresses HR.
See this image and copyright information in PMC

References

    1. Pandita TK, Hittelman WN. The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia-telangiectasia. Radiat Res. 1992;131(2):214–23. - PubMed (V体育2025版)
    1. Pandita TK, Hittelman WN. Initial chromosome damage but not DNA damage is greater in ataxia telangiectasia cells. Radiat Res. 1992;130(1):94–103. - VSports最新版本 - PubMed
    1. Scott SP, Pandita TK. The cellular control of DNA double-strand breaks. J Cell Biochem. 2006;99(6):1463–75. - "V体育ios版" PMC - PubMed
    1. Pandita TK, Richardson C. Chromatin remodeling finds its place in the DNA double-strand break response. Nucleic Acids Res. 2009;37(5):1363–77. - PMC - PubMed
    1. Kumar R, Horikoshi N, Singh M, Gupta A, Misra HS, Albuquerque K, et al. Chromatin modifications and the DNA damage response to ionizing radiation. Front Oncol. 2012;2:214. - PMC (VSports app下载) - PubMed

"VSports" Substances