2010年9月27日 · The tumor suppressor BRCA1, also phosphorylated by ATM/ATR kinases, is one of several proteins that colocalize with phospho-H2AX (γ-H2AX) at sites of active DNA repair. Both the precise mechanism and the purpose of BRCA1 …

2024年5月24日 · Here, by studying resistance to poly (ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication...

激活的ATM可以磷酸化CtIP（C-terminal-binding protein interacting protein），再与BRCA1（乳腺癌相关蛋白1）相互作用，形成BRCA1 / MRN / CtIP复合体，促进DNA末端切除，以形成单链DNA，从而促进 HR （同源重组）修复。

Here we show that BRCA1 and γ -H2AX form an acid-stable biochemical complex on chromatin after DNA damage. Maximal association of BRCA1 with γ -H2AX correlates with reduced global γ -H2AX levels on chromatin late in the repair process.

为了响应 DNA 损伤，H2AX 在丝氨酸残基 139 上磷酸化（称为 γH2AX），导致 DNA 修复效应器 53BP1 和 BRCA1 的募集。 在这里，通过研究 BRCA1/2 缺陷型乳腺肿瘤对聚（ADP-核糖）聚合酶（PARP）抑制剂的耐药性，我们确定了 γH2AX 在协调药物诱导的复制叉降解中的功能。 从机制上讲，γH2AX 驱动的复制叉降解是通过抑制 CtIP 介导的复制叉保护引起的。 因此，H2AX 丢失恢复了复制叉的稳定性，并增加了 BRCA1/2 缺陷肿瘤细胞的化疗耐药性，但没有恢复同源定 …

2024年5月24日 · In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug ...

2004年12月14日 · Male mice lacking full-length BRCA1 as a result of deletion of exon 11 (Brca1 Δ11/Δ11) are infertile due to a pachytene arrest; the pachytene cells have abnormal localization of phosphorylated H2AX (γH2AX) and sex body anomalies [8]. Together, these findings suggest an essential role for BRCA1 during the pachytene stage.

Most primary AML analyzed were characterized by low BRCA1 mRNA level and undetectable protein expression that likely contributed to explain their sensitivity to olaparib. Noteworthy, while PARP1 over-expression was detected in blasts not responsive to olaparib, phosphorylation of the histone H2AFX (γH2AX) was associated with drug sensitivity.

2015年3月1日 · AML blasts express undetectable BRCA1 protein. PARP1 and γH2AX are biomarkers to identify the response of AML to olaparib. Olaparib (AZD-2281, Ku-0059436) is an orally bioavailable and well-tolerated poly (ADP-ribose) polymerase (PARP) inhibitor currently under investigation in patients with solid tumors.

2015年8月1日 · In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients.