The 53BP1-EXPAND1 connection in chromatin structure regulation

Sy, Shirley M.-H.; Chen, Junjie; Huen, Michael S.Y.

doi:10.4161/nucl.1.6.13059

Cited by 10 publications

(10 citation statements)

References 17 publications

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“…Mammalian interphase chromatin also responds to DNA damage by altering the compactness of its architecture, thereby permitting local access of DNA repair machineries [56]. The PWWP domain-containing protein MUM1 (also known as EXPAND1) was recently reported to be an architectural component of chromatin, and by its direct interaction with 53BP1, MUM1 plays an accessory role to facilitate DNA damage-induced chromatin changes and is important for efficient DNA repair and cell survival following DNA damage [57].…”

Section: Reviewmentioning

confidence: 99%

Structure and function of the nucleosome-binding PWWP domain

Min

2014

Trends in Biochemical Sciences

178

133

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Section: Reviewmentioning

confidence: 99%

Structure and function of the nucleosome-binding PWWP domain

Min

2014

Trends in Biochemical Sciences

178

133

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“…This involves recruitment and activation of proteins that participate in DNA damage sensing, checkpoint signaling, chromatin remodeling, and DNA repair. The recruitment of DNA damage factors to sites of DNA damage is a complex and elaborate process, with different DNA damage factors recruited through distinct processes (Bekker‐Jensen et al , 2010; Sy et al , 2010). In response to DNA double‐strand breaks (DSBs), the Mre11/Rad50/NBS1 (MRN) complex detects DSBs and contributes to the recruitment and activation of the PI3K‐like kinase (PIKK) ATM (ataxia telangiectasia mutated) (Uziel et al , 2003; Falck et al , 2005; Lee and Paull, 2005).…”

Section: Introductionmentioning

confidence: 99%

Sumoylation of MDC1 is important for proper DNA damage response

et al. 2012

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In response to DNA damage, many DNA damage factors, such as MDC1 and 53BP1, redistribute to sites of DNA damage. The mechanism governing the turnover of these factors at DNA damage sites, however, remains enigmatic. Here, we show that MDC1 is sumoylated following DNA damage, and the sumoylation of MDC1 at Lys1840 is required for MDC1 degradation and removal of MDC1 and 53BP1 from sites of DNA damage. Sumoylated MDC1 is recognized and ubiquitinated by the SUMO-targeted E3 ubiquitin ligase RNF4. Mutation of the MDC1 Lys 1840 (K1840R) results in impaired CtIP, replication protein A, and Rad51 accumulation at sites of DNA damage and defective homologous recombination (HR). The HR defect caused by MDC1K1840R mutation could be rescued by 53BP1 downregulation. These results reveal the intricate dynamics governing the assembly and disassembly of DNA damage factors at sites of DNA damage for prompt response to DNA damage.

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“…Thus, it could be reasoned that the varied impact of 53BP1 on the DDR in earlier studies was affected by the nature of the lesion and its chromatin context. A recent search for 53BP1-interacting proteins identified the previously uncharacterized EXPAND1/MUM protein that mediates DNA damage-induced chromatin decon-densation (Sy and Huen 2010). This chromatin relaxation function of EXPAND is presumably mediated through its interaction with nucleosomes via its PWWP domain, a domain commonly found in chromatin-binding proteins (Huen et al 2010).…”

Section: Chromatin Changes That Promote Dsb Repairmentioning

confidence: 99%

Epigenetic regulation of genomic integrity

Deem

Tyler

2012

Chromosoma

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Inefficient and inaccurate repair of DNA damage is the principal cause of DNA mutations, chromosomal aberrations, and carcinogenesis. Numerous multiple-step DNA repair pathways exist whose deployment depends on the nature of the DNA lesion. Common to all eukaryotic DNA repair pathways is the need to unravel the compacted chromatin structure to facilitate access of the repair machinery to the DNA and restoration of the original chromatin state afterward. Accordingly, our cells utilize a plethora of coordinated mechanisms to locally open up the chromatin structure to reveal the underlying DNA sequence and to orchestrate the efficient and accurate repair of DNA lesions. Here we review changes to the chromatin structure that are intrinsic to the DNA damage response and the available mechanistic insight into how these chromatin changes facilitate distinct stages of the DNA damage repair pathways to maintain genomic stability.

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The 53BP1-EXPAND1 connection in chromatin structure regulation

Cited by 10 publications

References 17 publications

Structure and function of the nucleosome-binding PWWP domain

Structure and function of the nucleosome-binding PWWP domain

Sumoylation of MDC1 is important for proper DNA damage response

Epigenetic regulation of genomic integrity

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