RETRACTED: PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage.
RETRACTED: PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage.
复制标题
DOI：
10.1016/j.molcel.2014.05.030
复制
发表时间：
2014-06-19
期刊：
影响因子：
16
通讯作者：
D'Orazio, John A.
中科院分区：
文献类型：
--
作者：
Jarrett, Stuart G.;Horrell, Erin M. Wolf;Christian, Perry A.;Vanover, Jillian C.;Boulanger, Mary C.;Zou, Yue;D'Orazio, John A.
黑皮质素1受体（MC 1 R）通过cAMP发出信号，是一种黑素细胞跨膜受体，参与色素沉着、适应性晒黑和黑色素瘤抗性。我们报告MC 1 R介导的或药理学诱导的cAMP信号以cAMP依赖性蛋白激酶A（PKA）依赖的方式促进核苷酸切除修复（NER）。PKA直接磷酸化共济失调毛细血管扩张和Rad 3相关蛋白（ATR）的Ser 435，积极招募关键NER蛋白着色性干皮病互补组A（XPA）的网站的核紫外线光损伤，加速清除紫外线诱导的光损伤和减少诱变。ATR中Ser 435的缺失阻止PKA介导的ATR磷酸化，破坏ATR-XPA结合，延迟XPA向UV损伤的DNA的募集并提高UV诱导的诱变。这项研究将cAMP-PKA信号传导与NER联系起来，并说明了cAMP药理学拯救在MC 1 R缺陷、黑色素瘤易感个体中减少UV诱变的潜在益处。
The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic transmembrane receptor involved in pigmentation, adaptive tanning and melanoma resistance. We report MC1R-mediated or pharmacologically-induced cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435 which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA and elevates UV-induced mutagenesis. This study mechanistically links cAMP-PKA signaling to NER and illustrates potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals.
登录
查看更多内容
影响因子：
14.9
作者：
Kang TH;Reardon JT;Sancar A
通讯作者：
Sancar A
影响因子：
16
作者：
Liu S;Shiotani B;Lahiri M;Maréchal A;Tse A;Leung CC;Glover JN;Yang XH;Zou L
通讯作者：
Zou L
影响因子：
5.3
作者：
Jiang, GC;Sancar, A
通讯作者：
Sancar, A
影响因子：
11.2
作者：
Dong L;Wen J;Pier E;Zhang X;Zhang B;Dong F;Ziegler N;Mysz M;Armenta R;Cui R
通讯作者：
Cui R
影响因子：
4.7
作者：
Glaab, WE;Tindall, KR
通讯作者：
Tindall, KR