**Question:** After digestion by restriction endonucleases, DNA strands can be joined again by

A. DNA ligase
B. Topoisomerase
C. DNA polymerase
D. Thymidylate synthase

**Correct Answer:** A. DNA ligase

**Core Concept:** DNA ligase is an enzyme responsible for sealing the broken DNA ends created by restriction endonucleases, a type of enzyme used in molecular biology techniques like DNA cloning.

**Why the Correct Answer is Right:** DNA ligase (EC 6.5.1.1) is an essential enzyme in DNA repair and maintenance. It catalyzes the formation of phosphodiester bonds between 3'-hydroxyl and 5'-phosphate groups at the DNA ends, thereby sealing the breaks and restoring the integrity of the DNA molecule. This process is crucial for the success of molecular biology techniques like DNA cloning, as it allows the ligated DNA fragments to integrate into a host DNA molecule.

**Why Each Wrong Option is Incorrect:**

**Option A (DNA polymerase):** DNA polymerase is involved in DNA replication, not DNA repair or ligation. It adds nucleotides to the growing DNA strand, ensuring accurate replication.

**Option B (Topoisomerase):** Topoisomerase relieves the supercoiling stress in DNA by introducing or removing single-strand breaks, important for DNA replication and transcription. It is not involved in DNA ligation.

**Option D (Thymidylate synthase):** Thymidylate synthase is a key enzyme in the de novo synthesis of thymidylate nucleotides, which are essential for DNA synthesis during cell division. It is not involved in DNA ligation.

**Clinical Pearl:** Understanding the roles of different enzymes in DNA processing (ligation, replication, and repair) is essential for medical professionals, as it directly relates to genetic engineering, molecular biology, and gene therapy applications.