7.3: 긴 패치 염기 절제 복구

Long-patch Base Excision Repair
JoVE Core
Molecular Biology
This content is Free Access.
JoVE Core Molecular Biology
Long-patch Base Excision Repair

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01:02 min
November 23, 2020

Overview

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

  1. Lesion type: Depending on the type of base damage, a specific DNA glycosylase – mono or bifunctional, is recruited to the damaged site. While the sequential action of a monofunctional glycosylase favors long patch repair events, the bifunctional glycosylase drives short-patch BER.
  1. State of the cell cycle: The major protein participants that distinguish the long-patch BER from the alternative pathway of short-patch BER are proliferating cell nuclear antigen (PCNA), protein replication factor C (RF-C), and the flap structure-specific endonuclease 1 (FEN1). PCNA is particularly recognized as the lynchpin of this pathway. It acts both as the scaffold to anchor the polymerase at the damaged site and binds to FEN-1 to facilitate its nuclease activity. Furthermore, RF-C is required to load the PCNA onto the DNA. All of these proteins are also required during DNA replication, suggesting that long-patch BER mends damages to replicating DNA while short-patch is used for repairing resting DNA.
  1. ATP shortage: It has also been observed that while single nucleotide or short patch BER predominates under normal physiological conditions, under conditions of ATP shortage, the preference is shifted towards long-patch BER. This is because poly(ADP-ribose) can serve as a unique source of ATP during the ligation step in BER.

Transcript

포유류에서는 두 번째 유형의 BER이 관찰되며, 이는 ATP 부족 기간 동안 우선적으로 사용되는 긴 패치 BER입니다. 긴 패치 BER은 손상된 단일 염기를 제거하는 대신 여러 뉴클레오티드 길이의 패치를 복구합니다.

이를 달성하기 위해 다른 DNA 중합효소인 δ/ɛ는 원래 뉴클레오티드를 대체하는 여러 뉴클레오티드를 추가합니다. 이로 인해 플랩(flap)이라고 하는 올리고뉴클레오티드가 돌출되어 손상된 염기가 포함됩니다.

증식 세포 핵 항원(Proliferating Cell Nuclear Antigen, PCNA)이라고 하는 복제 인자(replication factor)가 있는 경우, 플랩 엔도뉴클레아제(Flap Endonuclease, FEN)라고 하는 특수 엔도뉴클레아제(Flap Endonuclease)가 DNA 리가아제(ligase)가 흠집을 밀봉하기 전에 이 플랩을 제거합니다.

긴 패치 BER의 메커니즘은 전리 방사선으로 인한 손상을 복구하는 데 특히 유용합니다.

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