Division of Labor between PCNA Loaders in DNA Replication and Sister Chromatid Cohesion Establishment

被引：42

作者：

Liu, Hon Wing ^{[1
]}

Bouchoux, Celine ^{[1
]}

Panarotto, Melanie ^{[1
]}

Kakui, Yasutaka ^{[1
]}

Patel, Harshil ^{[2
]}

Uhlmann, Frank ^{[1
]}

机构：

[1] Francis Crick Inst, Chromosome Segregat Lab, 1 Midland Rd, London NW1 1AT, England

[2] Francis Crick Inst, Bioinformat & Biostat Sci Technol Platform, 1 Midland Rd, London NW1 1AT, England

来源：

MOLECULAR CELL | 2020年 / 78卷 / 04期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

CELL NUCLEAR ANTIGEN; STRAND-SPECIFIC ANALYSIS; FACTOR-C; POLYMERASE EPSILON; GENOME-WIDE; BUDDING YEAST; COMPLEX; CTF18; RFC; ACETYLATION;

D O I：

10.1016/j.molcel.2020.03.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Several replication-fork-associated "cohesion establishment factors,'' including the multifunctional Ctf18-RFC complex, aid this process in as yet unknown ways. Here, we show that Ctf18-RFC's role in sister chromatid cohesion correlates with PCNA loading but is separable from its role in the replication checkpoint. Ctf18-RFC loads PCNA with a slight preference for the leading strand, which is dispensable for DNA replication. Conversely, the canonical Rfc1-RFC complex preferentially loads PCNA onto the lagging strand, which is crucial for DNA replication but dispensable for sister chromatid cohesion. The downstream effector of Ctf18-RFC is cohesin acetylation, which we place toward a late step during replication maturation. Our results suggest that Ctf18-RFC enriches and balances PCNA levels at the replication fork, beyond the needs of DNA replication, to promote establishment of sister chromatid cohesion and possibly other post-replicative processes.

引用

页码：725 / +

页数：18

共 74 条

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