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Review
. 2021 Nov 1;49(5):2133-2141.
doi: 10.1042/BST20210161.

Efficiency and equity in origin licensing to ensure complete DNA replication

Liu Mei  1 , Jeanette Gowen Cook  1
Affiliations
Review

Efficiency and equity in origin licensing to ensure complete DNA replication

Liu Mei et al. Biochem Soc Trans. .

Abstract

The cell division cycle must be strictly regulated during both development and adult maintenance, and efficient and well-controlled DNA replication is a key event in the cell cycle. DNA replication origins are prepared in G1 phase of the cell cycle in a process known as origin licensing which is essential for DNA replication initiation in the subsequent S phase. Appropriate origin licensing includes: (1) Licensing enough origins at adequate origin licensing speed to complete licensing before G1 phase ends; (2) Licensing origins such that they are well-distributed on all chromosomes. Both aspects of licensing are critical for replication efficiency and accuracy. In this minireview, we will discuss recent advances in defining how origin licensing speed and distribution are critical to ensure DNA replication completion and genome stability.

Keywords: DNA replication and recombination; cell cycle; genome integrity.

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Figures

Fig 1.
Fig 1.. Origin licensing in the cell cycle
(A) Diagram of the sequence of events that occur as each origin is licensed. ORC selects the sites and bind to DNA, CDC6 and CDT1 are recruited, then direct the loading of MCM. (B) Origin licensing starts in late mitosis and continues throughout G1 phase. The loaded MCM complexes become the core of active DNA helicases and unwind DNA and then are unloaded once replication is finished in S phase. After S phase begins, no new origin licensing is allowed.
Fig 2.
Fig 2.. Origin licensing speed
(A) Origin licensing in normal cells. Origin licensing is unidirectional in G1 phase, the loaded MCM complexes won’t be unloaded until S phase. (B) Origin licensing in cells with short G1 length. If cells license origins with the same speed as in cells with long G1 phases (indicated with red line), cells will experience under-licensing at S phase entry. If cells license in a short G1, they will avoid under-licensing (indicated with blue line).
Fig 3.
Fig 3.. Origin licensing distribution
(A) Adequate distribution of licensed origins (loaded MCM complexes). The DNA replication is successful in the subsequent S phase. (B) Inappropriate MCM loading distribution elevates the risk of under-replication in S phase.
See this image and copyright information in PMC

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