Mayer M L, Gygi S P, Aebersold R, Hieter P
Graduate Program in Biochemistry, Cellular and Molecular Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Mol Cell. 2001 May;7(5):959-70. doi: 10.1016/s1097-2765(01)00254-4.
We have identified and characterized an alternative RFC complex RFC(Ctf18p, Ctf8p, Dcc1p) that is required for sister chromatid cohesion and faithful chromosome transmission. Ctf18p, Ctf8p, and Dcc1p interact physically in a complex with Rfc2p, Rfc3p, Rfc4p, and Rfc5p but not with Rfc1p or Rad24p. Deletion of CTF18, CTF8, or DCC1 singly or in combination (ctf18Deltactf8Deltadcc1Delta) leads to sensitivity to microtubule depolymerizing drugs and a severe sister chromatid cohesion defect. Furthermore, temperature-sensitive mutations in RFC4 result in precocious sister chromatid separation. Our results highlight a novel function of the RFC proteins and support a model in which sister chromatid cohesion is established at the replication fork via a polymerase switching mechanism and a replication-coupled remodeling of chromatin.
我们已经鉴定并表征了一种替代的复制因子C复合物RFC(Ctf18p、Ctf8p、Dcc1p),它是姐妹染色单体黏连和染色体忠实传递所必需的。Ctf18p、Ctf8p和Dcc1p在一个复合物中与Rfc2p、Rfc3p、Rfc4p和Rfc5p发生物理相互作用,但不与Rfc1p或Rad24p相互作用。单独或联合缺失CTF18、CTF8或DCC1(ctf18Δctf8Δdcc1Δ)会导致对微管解聚药物敏感以及严重的姐妹染色单体黏连缺陷。此外,RFC4中的温度敏感突变会导致姐妹染色单体过早分离。我们的结果突出了复制因子C蛋白的一种新功能,并支持了一个模型,即通过聚合酶切换机制和染色质的复制偶联重塑在复制叉处建立姐妹染色单体黏连。