Abstract
DNA packs into highly condensed chromatin to organize the genome in eukaryotes but occludes many regulatory DNA elements. Access to DNA within nucleosomes is therefore required for a variety of biological processes in cells including transcription, replication, and DNA repair. To cope with this problem, cells employ a set of specialized ATP-dependent chromatin-remodeling protein complexes to enable dynamic access to packaged DNA. In the present review, we summarize the recent advances in the functional and mechanistic studies on a particular chromatin remodeler SMARCAD1Fun30 which has been demonstrated to play a key role in distinct cellular processes and gained much attention in recent years. Focus is given to how SMARCAD1Fun30 regulates various cellular processes through its chromatin remodeling activity, and especially the regulatory role of SMARCAD1Fun30 in gene expression control, maintenance and establishment of heterochromatin, and DNA damage repair. Moreover, we review the studies on the molecular mechanism of SMARCAD1Fun30 that promotes the DNA end-resection on double-strand break ends, including the mechanisms of recruitment, activity regulation and chromatin remodeling.
Highlights
INTRODUCTIONDNA is highly packaged to form chromatin. Nucleosomes are the basic units of chromatin, consisting of roughly 1.75 super-helical turns of DNA wrapped around octamers composed of four core histones: one histone H3-H4 tetramer and two histone H2A-H2B dimers (Kornberg, 1974; Kornberg and Thomas, 1974)
In eukaryotes, DNA is highly packaged to form chromatin
Despite the surprising similarities in the function of SMARCAD1 in different cellular processes, the different locations of SMARCAD1 lead to different roles, such as evicting nucleosomes during resection but stabilizing nucleosomes during DNA replication
Summary
DNA is highly packaged to form chromatin. Nucleosomes are the basic units of chromatin, consisting of roughly 1.75 super-helical turns of DNA wrapped around octamers composed of four core histones: one histone H3-H4 tetramer and two histone H2A-H2B dimers (Kornberg, 1974; Kornberg and Thomas, 1974). Bantele et al (2017) proposed a regulatory model that Fun antagonizes the binding of Rad at the DSB sites by occupying the two binding sites of nucleosomes and Dbp11 This antagonism is dependent on its chromatin remodeling enzyme activity, because mutations in the active site of ATPase, whether in humans or yeast, caused DNA end-resection defects (Chen X. et al, 2012; Chakraborty et al, 2018). SMARCAD1 may recognize BRCA1-BARD1catalyzed histone H2A (K125/127/129) ubiquitination through its CUE domain to locate at the DSB sites and promote the DNA end-resection (Figure 3B) Such a mechanism is unlikely to be an evolutionary conserved (Chen X. et al, 2012; Pfander and Bantele, 2019). The recruitment of SMARCAD1Fun may be the result of a combination of factors, which need to be further studied
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