Interaction of BARD1 and HP1 Is Required for BRCA1 Retention at Sites of DNA Damage

Wu, Wenwen; Nishikawa, Hiroyuki; Fukuda, Takayo; Vittal, Vinayak; Asano, Masahide; Miyoshi, Yasuo; Klevit, Rachel E.; Ohta, Tomohiko

doi:10.1158/0008-5472.can-14-2796

Cited by 91 publications

(121 citation statements)

References 53 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…In addition, H3K9me2/3 demethylases KDM4B and KDM4D are recruited to the DNA damage sites mediated by PARP1, and are responsible for H3K9 demethylation (Khoury-Haddad et al, 2014;Young et al, 2013). However, a recent study reveals that H3K9me2 is required for BARD1 and BRCA1 retention at sites of DNA damage, thus promoting HR repair in S phase of cell cycle (Wu et al, 2015). It indicates that H3K9me3 is removed, but H3K9me2 is reserved at damaged DNA.…”

Section: Methylationmentioning

confidence: 99%

Histone modifications in DNA damage response

Cao

Shen

Zhu

2016

Sci. China Life Sci.

View full text Add to dashboard Cite

DNA damage is a relatively common event in eukaryotic cell and may lead to genetic mutation and even cancer. DNA damage induces cellular responses that enable the cell either to repair the damaged DNA or cope with the damage in an appropriate way. Histone proteins are also the fundamental building blocks of eukaryotic chromatin besides DNA, and many types of post-translational modifications often occur on tails of histones. Although the function of these modifications has remained elusive, there is ever-growing studies suggest that histone modifications play vital roles in several chromatin-based processes, such as DNA damage response. In this review, we will discuss the main histone modifications, and their functions in DNA damage response.DNA damage response, histone modifications, chromatin, DNA repair Citation:

show abstract

Section: Methylationmentioning

confidence: 99%

Histone modifications in DNA damage response

Cao

Shen

Zhu

2016

Sci. China Life Sci.

View full text Add to dashboard Cite

show abstract

“…The BARD1 BRCT repeats were reported to interact with poly(ADP) ribose (13) and more recently to specifically recognize histone H3 dimethylated at Lys 9 (H3K9me2) through its interaction with HP1 proteins.14 This interaction was reported to anchor BRCA1-BARD1 at DNA damage sites (14). Genetically, the BRCA1-BARD1 interaction is unique in the BRCA1 network in that it appears to be necessary for the majority of BRCA1 in vivo function.…”

Section: Connecting Brca Network Biochemistry To the Ddrmentioning

confidence: 99%

Deciphering the BRCA1 Tumor Suppressor Network

Jiang

Greenberg

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

The BRCA1 tumor suppressor protein is a central constituent of several distinct macromolecular protein complexes that execute homology-directed DNA damage repair and cell cycle checkpoints. Recent years have borne witness to an exciting phase of discovery at the basic molecular level for how this network of DNA repair proteins acts to maintain genome stability and suppress cancer. The clinical dividends of this investment are now being realized with the approval of first-in-class BRCAtargeted therapies for ovarian cancer and identification of molecular events that determine responsiveness to these agents. Further delineation of the basic science underlying BRCA network function holds promise to maximally exploit genome instability for hereditary and sporadic cancer therapy.The breast cancer early-onset genes BRCA1 and BRCA2 were discovered by positional cloning approaches in kindreds with a high prevalence of breast and ovarian cancer. The initial lack of clarity presented by the domain structure of the proteins was remedied by a series of discoveries that revealed the proteins biochemically interact in large nuclear foci in response to DNA damage and are required to execute homology-directed DNA repair and cell cycle checkpoints (1). These observations strongly suggested that a common function in genome integrity maintenance is necessary to suppress cancer. Subsequent advances in protein purification and mass spectrometry methodologies have led to the expansion of this concept with the discovery that at least 13 different tumor suppressor proteins interact with BRCA1 and BRCA2. Despite these striking similarities, a linear model of BRCA-dependent DNA repair and tumor suppression is challenged by multiple other observations, namely, only ϳ5% of each protein exists in association with the BRCA1-BRCA2 complex, and breast cancers occurring in individuals with germ-line BRCA1 or BRCA2 mutations typically display different histopathologies and gene expression profiles. Coupled with the realization that chemoresistance mechanisms in BRCA1 and BRCA2 mutant cancers also differ, these features have inspired a network model relating BRCA molecular function in DNA repair to tumor suppression. We highlight recent insights into the BRCA tumor suppressor network and stress the connections between basic molecular knowledge of these proteins and their roles in genome integrity, tumor suppression, and response to therapy.

show abstract

“…7,8,[37][38][39] BRCA1 tBRCT domain is responsible for promoting protein-protein interactions, mediating the recruitment and retention at the DSB sites. 35,36 During the DNA repair signaling, as DDR-related proteins are recruited to DSB sites, they accumulate and can be visualized as nuclear foci.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 recruitment to damaged DNA sites is dependent on CDK9

et al. 2017

View full text Add to dashboard Cite

Double strand break lesions, the most toxic type of DNA damage, are repaired primarily through 2 distinct pathways: homology-directed recombination (HR) and non-homologous end-joining (NHEJ). BRCA1 and 53BP1, 2 proteins containing the BRCT modular domain, play an important role in DNA damage response (DDR) by orchestrating the decision between HR and NHEJ, but the precise mechanisms regarding both pathways are not entirely understood. Previously, our group identified a putative interaction between BRCA1 and BARD1 (BRCA1-associated RING domain 1) and the cyclin-dependent kinase (CDK9). CDK9 is a component of the positive transcription elongation complex and has been implicated in genome integrity maintenance associated with the replication stress response. Here we show that CDK9 interacts with endogenous BRCA1 and BARD1 mediated by their RING finger and BRCT domains, and describe CDK9 ionizing radiation-induced foci (IRIF) formation and its co-localization with BRCA1 in DNA damage sites. Cells lacking CDK9 are characterized by an altered g¡H2AX foci dynamics after DNA damage, a reduced efficiency in HR but not in NHEJ repair, failure to form BRCA1 and RAD51 IRIF and increased sensitivity to genotoxic agents. These data indicate that CDK9 is a player in the DDR and is consistent with its participation in HR pathway by modulating BRCA1 response.

show abstract

Interaction of BARD1 and HP1 Is Required for BRCA1 Retention at Sites of DNA Damage

Cited by 91 publications

References 53 publications

Histone modifications in DNA damage response

Histone modifications in DNA damage response

Deciphering the BRCA1 Tumor Suppressor Network

BRCA1 recruitment to damaged DNA sites is dependent on CDK9

Contact Info

Product

Resources

About