Advances in SUMO-based regulation of homologous recombination

Abstract

Homologous Recombination (HR) is a critical DNA repair mechanism for a range of genome lesions. HR is responsible for mending DNA double strand breaks (DSBs) using intact template DNA. In addition, many HR proteins help cope with DNA lesions generated from DNA replication and telomere deficiency. The functions of HR proteins are often regulated by protein modifications that can quickly and reversibly adjust substrate proteins' attributes. Sumoylation is one of the prevalent modifications that affects all steps of the HR processes and exerts diverse regulation on substrates. This review aims to summarize the most recent advances in our understanding of SUMO-based HR regulation and highlight some key questions that remain to be elucidated.

Figure 1:. Overview of sumoylation and its effects on Homologous Recombination (HR) proteins.

A) Schematic of the SUMO pathway. Precursor SUMO is matured into conjugatable SUMO by specialized proteases, Ulp1 in yeast and SENPs in higher eukaryotes. Following the sequential action of the SUMO E1 activating enzyme, the SUMO E2 conjugating enzyme and a SUMO E3 ligase, SUMO is covalently conjugated to the lysine(s) of the substrate. A substrate can by mono-, multi-, or poly-sumoylated. Sumoylation can be reversed by desumoylation proteases. Poly- or multi-sumoylated proteins can also be targeted for ubiquitination and degradation by the STUbL enzymes or be removed from DNA or protein complexes by the segregase. (B) Sumoylation regulates HR. This review outlines the most recent progress in understanding SUMO-based regulation, such as end resection of double strand breaks, processing of HR intermediates, and relocation of collapsed replication forks to the nuclear pore complexes.