Oncoprotein Tudor-SN is a key determinant providing survival advantage under DNA damaging stress

Abstract

Herein, Tudor-SN was identified as a DNA damage response (DDR)-related protein that plays important roles in the early stage of DDR. X-ray or laser irradiation could evoke the accumulation of Tudor-SN to DNA damage sites in a poly(ADP-ribosyl)ation-dependent manner via interaction with PARP-1. Additionally, we illustrated that the SN domain of Tudor-SN mediated the association of these two proteins. The accumulated Tudor-SN further recruited SMARCA5 (ATP-dependent chromatin remodeller) and GCN5 (histone acetyltransferase) to DNA damage sites, resulting in chromatin relaxation, and consequently activating the ATM kinase and downstream DNA repair signalling pathways to promote cell survival. Consistently, the loss-of-function of Tudor-SN attenuated the enrichment of SMARCA5, GCN5 and acetylation of histone H3 (acH3) at DNA break sites and abolished chromatin relaxation; as a result, the cells exhibited DNA repair and cell survival deficiency. As Tudor-SN protein is highly expressed in different tumours, it is likely to be involved in the radioresistance of cancer treatment.

The multifaceted oncogene SND1 in cancer: focus on hepatocellular carcinoma

“…However, the functional consequence of this observation is yet to be elucidated. In response to DNA damage, SND1 is recruited to the damage site by Poly ADP-ribose polymerase 1 (PARP-1), a DNA damage sensor [51] . The accumulated SND1 recruits to the damage site ATP-dependent chromatin remodeler (ARCA5) and histone acetyltransferase (GCN5), two enzymes that promote chromatin relaxation to enable access of DNA damage response related proteins to the damage site.…”

Global Tudor‐SN transgenic mice are protected from obesity‐induced hepatic steatosis and insulin resistance

“…Tudor-staphylococcal nuclease (SN), also known as staphylococcal nuclease domain containing 1 (Snd1), is a highly conserved and ubiquitously expressed multifunctional protein (15)(16)(17)(18)(19)(20)(21)(22)(23). This enzyme comprises a tandem repeat of 4 SN-like domains (referred to as SN domains) at the N terminus and a fusion of a Tudor domain with a partial SN domain at the C terminus (referred to as a TSN domain) (22).…”

“…This enzyme comprises a tandem repeat of 4 SN-like domains (referred to as SN domains) at the N terminus and a fusion of a Tudor domain with a partial SN domain at the C terminus (referred to as a TSN domain) (22). Tudor-SN is normally localized in the cytoplasm except under certain circumstances, such as stress, in which it may shuttle between the nucleus and the cytoplasm (16,19,23). This protein plays important roles in the early stage of the DNA damage response in a poly-ADP-ribosylation-dependent manner via interaction with poly (ADP-ribose) polymerase (Parp)-1 through an SN domain (23).…”

“…Tudor-SN is normally localized in the cytoplasm except under certain circumstances, such as stress, in which it may shuttle between the nucleus and the cytoplasm (16,19,23). This protein plays important roles in the early stage of the DNA damage response in a poly-ADP-ribosylation-dependent manner via interaction with poly (ADP-ribose) polymerase (Parp)-1 through an SN domain (23). Tudor-SN, which is indispensable for normal development, promotes cell-cycle progression by facilitating E2F-1-mediated gene transcription (17).…”

The interactome of the prostate-specific protein Anoctamin 7

“…The expression of SND1 is increased in many cancers, including PrCa. Similar to HSPA1A, SND1 is associated with development of resistance to cancer therapies [41,42]. This is the first study in which ANO7 interactions have been investigated.…”